Titles link to slides when available. Please note: Presentations given at CINF symposia have been posted to the CINF website with express permission granted by the authors who retain the original copyright. These presentations are for information purposes only and cannot be further disseminated without the author's prior written permission.
CINF
1: Where we've come from and where we're going
Lorrin R. Garson, Publications Division, American Chemical Society
(retired), 1155 Sixteenth Street, N.W, Washington, DC 20036, 9929garson@verizon.net
Abstract
The development of electronic communications starting in the mid 19th
century, followed by the advent of computers in the mid 20th century has led
to the nearly ubiquitous electronic availability of chemical information at
the start of the 21st century. At present, the great majority of scientific
journals are available online. Some of the key events that led to the
development of electronic journals, challenges facing
scientific-technical-medical publishing, and what the scientific community
can expect in the near future will be discussed.
CINF 2: State of electronic publishing today: Tools, trends, and
technology
Barry Bealer, Really Strategies Inc, 618 South Broad Street, 2nd
Floor, Lansdale, PA 19446, Fax: 215-631-9358, bbealer@reallysi.com
Abstract
Publishers face many challenges when producing electronic content and
products. Today, publishers accept the fact that content plus technology
equals value and that growth from digital products will continue to increase
revenue. However, digital products operate under a different set of
assumptions and business models than print products. A variety of enticing
tools, technology, and trends can enamor publishers as they forge into
electronic publishing initiatives. Identifying what is hype and what is
publishing reality in specific publishing environments is key to seeing a
return on technology investment. Really Strategies is a full service firm
that helps publishers bring strategy, content, and technology together.
CINF 3: Journal of Chemical Education Digital Library
Jon L. Holmes, Journal of Chemical Education, University of
Wisconsin-Madison, 209 N. Brooks St., Madison, WI 53715-1116, Fax:
608-262-7145, and J.W. Moore, Department of Chemistry, University of
Wisconsin-Madison
Abstract
The Journal of Chemical Education has a long tradition of providing
chemistry teachers with the information they need to perform their craft.
Extending that tradition into the digital realm of the Internet has posed
some challenges. To help meet those challenges, JCE has joined with
the National Science Digital Library (NSDL) project of the NSF and is
building the JCE Digital Library.
Developing a digital library collection has taught JCE, the
publisher, several lessons in how to play the role of a library. The lessons
include: choosing a meta data standard, developing a controlled vocabulary
for our meta data; making decisions about the granularity of our meta data,
devising a system for integrating the assignment of meta data into our
publishing workflow, deploying a system to make our meta data available to
meta data repositories, and constructing a new area of JCE Online,
the JCE WWW site, to house our collection.
Here, we will discuss the challenges of constructing a digital library
collection and present our solutions to some of the problems we have
encountered along the way. We will look at the process of constructing a
library collection from the perspective of a small publisher of an academic
journal.
CINF 4: Document acquisition: Lessons learned in providing the ChemPort
linking service
Stephen A. Renner, CAS, 2540 Olentangy River Road, Columbus, OH
43202-1505, Fax: 614-447-5470, srenner@cas.org
Abstract
It is no secret that the world of STM scholarly publishing is in turmoil. It
is a chaotic mix of electronic full text, myriad purchasing arrangements,
A&I databases, search engines, visualization features, portals, link
resolvers, new terminology such as "DOI" and "SFX," new library automation
software, new standards and protocols, and associated client/server and
client-based applications. Amidst this chaos one constant from the print era
remains: the need for the scientist to obtain copies of journal articles and
patents of interest. CAS introduced the ChemPort full-text linking service
in 1997 with the mission of "connecting the user to electronic full text at
the publishers' sites." We soon learned that the linking scientists to full
text at publishers' sites is only one of many ways, and sometimes not the
best way, to help scientists and information professionals obtain documents.
This presentation will share the challenges and lessons learned in building
and operating ChemPort to meet the needs of scientists, information
professionals, librarians, and publishers, and will glimpse into the future
of document acquisition.
CINF 5: 25 Year trends in information seeking and
reading patterns of chemists
Donald W. King, University of Pittsburgh School of Information
Sciences, Sara Fine Institute for Interpersonal Behavior & Technology, 600
IS Building, 135 North Bellefield Avenue, Pittsburgh, PA 15260, dwking@pitt.edu,
and Carol Tenopir, School of Information Sciences, College of Communication
and Information, University of Tennessee
Abstract
This paper presents evidence of chemists' information seeking and reading
patterns observed by extracting chemists' survey responses from 42
readership surveys conducted over the past 25 years. In particular, trends
show changes in how chemists learn about articles read, where they obtain
them and the format of these articles. Five surveys conducted since 2000
show the appreciable changes brought about by the emergence of electronic
journals. The survey results also show the usefulness and value of reading
scholarly journal articles.
CINF 6: Chemists online: Analysis of usage statistics and referral URLs
of ACS electronic journals
Philip M. Davis and Leah R. Solla, Collection Development, Cornell
University, Mann Library, Ithaca, NY 14850-2501, Fax: 607-255-0318, pmd8@cornell.edu,
lrm1@cornell.edu
Abstract
Publishers and librarians are increasingly interested in measuring the use
of electronic journals. Most usage reports, however, provide only the
aggregate number of article requests, and tell us very little about
individual user behavior. This presentation will summarize two recent
studies using IP-level data to represent individual user behavior. The first
study describes the distribution of ACS article downloads over a university
community, and suggests that the majority of requests come from a small
number of users. The second study details how scientists were referred to
ACS articles using a transaction log analysis and indicates that while
individuals tend to use few methods to link to articles, collectively
researchers utilize many different pathways to access the same literature.
These studies represent non-obtrusive methods to better understand the
information seeking and usage behavior of chemists.
CINF 7: SPARC: Model projects and strategies for
changing the scholarly communication system
Julia C. Blixrud, Scholarly Publishing and Academic Resources
Coalition, 21 Dupont Circle, Ste 800, Washington, DC 20036, Fax:
785-841-5576, jblix@arl.org
Abstract
The Scholarly Publishing and Academic Resources Coalition (SPARC) has been
providing support for new models of scholarly communication since 1998.
Several projects have reached maturity and can be evaluated as to their
success. Others are still in development, but have been based on experiences
gained by those who have preceded them in the use of new technologies as
well as new business models needed to transform scholarly communication.
This presentation will summarize some of SPARC's projects and examine
whether they are achieving their stated objectives. Other, non-SPARC
electronic projects also will be reviewed to determine how they are changing
the nature of scholarly and scientific communication. Patterns determining
successful projects will be identified.
CINF 8: Results of survey: Academic efforts to
address the scholarly communications crisis
Randall K. Ward1, David J. Michaelis2, Robert
Murdoch3, Brian Roberts3, and Julia C. Blixrud4.
(1) Harold B. Lee Library, Brigham Young University, 2320 HBLL, Provo, UT
84602, Fax: 801-422-0466, randy_ward@byu.edu, (2) Chemistry and
Biochemistry, Brigham Young University, (3) Lee Library, Brigham Young
University, (4) Scholarly Publishing and Academic Resources Coalition (SPARC),
American Research Libraries
Abstract
During the 2002-03 school year a nationwide telephone survey of academic
institutions was conducted from Brigham Young University to determine the
extent of efforts in addressing the “scholarly communications crisis”, often
characterized as the spiraling costs of scholarly journals. 170 universities
were surveyed (all were members of the Scholarly Publishing and Academic
Resources Coalition). Presented will be the statistical results of the
20-question survey along with some commonly mentioned anecdotal
recommendations. The statistics gathered can serve as a benchmark for
progress in addressing the crisis if the survey were repeated.
CINF 9: Change as opportunity
Grace Baysinger, Swain Library of Chemistry and Chemical Engineering,
Stanford University Libraries, 364 Lomita Drive, Organic Chemistry Building,
Stanford, CA 94305-5080, Fax: 650-725-2274, graceb@stanford.edu
Abstract
Large academic research libraries are experiencing major changes in
collections, staffing, facilities, and infrastructure. While reviews and
re-examination are healthy, the rate of change that is occurring is both
invigorating and humbling. While most library and information science
programs introduce students to topics such as management and building
library collections, few programs focus on the complexities facing science
libraries and the rapid evolution that is occurring in them. Thus,
mentoring, collaborating, and communicating with colleagues is vital for a
successful career as a science information specialist. Understanding the
culture of an institution and finding ways to influence decisions is
essential. Taking leadership roles locally and nationally in professional
organizations such as ACS enables participants to better understand,
support, and shape these environments. This presentation will highlight some
of the changes that are occurring in large academic research libraries and
opportunities that are happening as a result of these changes.
CINF 10: New latitude and attitude in the information industry
Suzan Brown, Vice President, Marketing and Sales, Chemical Abstract
Service, 2540 Olentangy River Road, Columbus, OH 43202, sbrown@cas.org
Abstract
Chemistry, like the other physical sciences, began as an activity dominated
by male practitioners, which is perhaps a reflection of the cultural and
educational norms that prevailed over the centuries of scientific
development. In any case, the demographics of professional chemists have
changed slowly but steadily toward greater inclusiveness. By contrast, women
have been better represented in the information profession and in electronic
publishing in general. What obstacles, advantages, and opportunities does
the marketing of information and electronic publishing offer women today?
The experience and impressions of one female marketing executive who has
worked for two prominent information providers serving very different
markets, Mead Data Central and CAS. These experiences may be representative
or at the very least informative for individuals considering a career in
this field.
CINF 11: The
degree is only the first step in reaching for the stars
Lori Kumar, VP Oral Care R&D, Pfizer Inc, 201 Tabor Road, Morris
Plains, NJ 07950, lori.kumar@pfizer.com
Abstract
Dr. Lori Kumar has over 18 years experience in various leadership roles at
Pfizer Consumer Healthcare located in New Jersey. She began her career as a
scientist and gradually progressed to her current position as the vice
president of oral care research and development, overseeing all global
research and development.
She led the development of major new oral care products such as Listerine
PocketPaks, Tartar Control Listerine and most recently Natural Citrus
Listerine Mouthwash. From the laboratory bench to leadership positions in
research, she has been actively involved in every phase of the product,
including inception through commercialization. Lori also leads the clinical
group which develops and supports new claims for existing, as well as, new
oral care products under development. Her team’s most recent accomplishments
include proving that “Listerine is as effective as flossing”.
Lori received her Ph.D. in Analytical Chemistry from New Mexico State
University.
CINF 12: Allowing serendipity in your career planning
Tracy C. Williamson, Office of Pollution Prevention and Toxics
(7406), U.S. Environmental Protection Agency, 401 M. Street, SW, Washington,
DC 20460, Fax: 202-260-0816
Abstract
The speaker will describe her education path and career choices, both
planned and serendipitous, from college to graduate school to a staff
chemist then a manager in the Federal Government. She will discuss her
current job responsibilities at her place of employment, the US EPA. She
will also describe the career challenges and opportunities for woman
scientists at the US EPA and across the Federal Government. This will
include a discussion of technical assignments, intra- and inter-agency
collaborative opportunities, academic and industry partnerships, and
international programs.
CINF 13: Chemistry: A solid foundation for
alternative careers
Janice L. Fleming, V.P., Planning & Development, Cadmus
KnowledgeWorks, 940 Elkridge Landing Road, Linthicum, MD 21010, flemingj@cadmus.com
Abstract
Career directions can change for a variety of reasons and our core skills
and talents as chemists actually prepare us in many ways for alternative
careers. Some of the skills I've found to be most valued by employers will
be highlighted. Many were based in my chemistry background, while others
were developed with time and attention. I'll also address the career
transition process when it involves stepping into new career areas. The
connections from one job to the next may surprise you, and how little you
really need to know initially about the work at hand might surprise you even
more. Your deeper value is often tied to the skills and creativity borne
from your chemical education and training.
CINF 14: Can editorial peer review survive in a
digital environment?
Ann C. Weller, Library of the Health Sciences, University of Illinois
at Chicago, 1750 W. Polk St., Chicago, IL 60612, Fax: 312-996-9584, acw@uic.edu
Abstract
The digital environment presents the opportunity for scientists to obtain
electronic access to research output through a number of nontraditional
routes: institutional repositories, researchers’ websites, or journals whose
contents are freely available online. Some options present challenges for
journals that traditionally published research results after vetting through
the editorial peer review process. In addition to preservation and
authentication of electronic information, electronic publishers must also
assure the integrity of the research results themselves. New publishing
endeavors like PubMed Central, physics e-prints, and SPARC (e.g., Organic
Letters) may all impact the peer review process. This paper will focus on
several aspects of peer review in this new environment: review the standard
model, present some working examples of alternatives to the traditional
model, evaluate some proposed models, examine the potential impact of
electronic publishing, and speculate about the future of peer review and
scientific publishing.
CINF 15: Peer review in the Open Access era
(see also
here)
Stevan Harnad, Centre de neuroscience cognitive, Universite du Québec
à Montréal, Montreal, QC H3C 3P8, Fax: 514-987-8952, harnad@uqam.ca
Abstract
Classical peer review will not change in its
essentials in the online/open-access age, but it will become
faster, cheaper and more efficient to implement. Papers will be
submitted by depositing them in the journal's website or the author's
institutional website. Many authors will elect to make their preprints
publicly accessible, either on the journal's website or on their
institutional website. Referee selection will be aided by online
searches of the
open-access literature and sometimes by calls-for-referees to targetted
specialist lists. Referees will access the manuscripts online and submit
their reports online, and editorial dispositions will be done online.
Self-selected commentary may sometimes supplement (but not substitute for)
the editor-appointed refereed. After publication, a
similar system can be used for open
peer commentary, and authors' responses. Article
download and citation impact
will be tracked from the preprint onward by online scientometric engines.
CINF 16: Peer review is the worst form of
manuscript assessment except for all the other forms that have been tried
Wendy A Warr, Wendy Warr & Associates, 6 Berwick Court, Holmes
Chapel, Cheshire CW4 7HZ, United Kingdom, Fax: 011 44 1477 533837
Abstract
"High quality, high impact" is the current mantra of ACS Publications but
how does an editor define "high quality" and ensure that high standards are
maintained? Peer review is only one part of the quality control process but
it is the critical first step and it is inevitably subjective. Editors are
only human and so are their reviewers. While protecting reviewers’
anonymity, this paper will briefly examine some of the practices and foibles
of an editor and her reviewers, and will outline some lessons learned over
the years. Early results of a more general study of the strengths and
weaknesses of peer review in chemistry publishing will also be reported.
With apologies to Winston Churchill, "No-one pretends that peer review is
perfect or all-wise. Indeed...peer review is the worst form of assessment
except for all the other forms that have been tried".
CINF 17: Scientific quality assurance by
interactive peer review and public discussion
Ulrich Pöschl1, Kenneth S. Carslaw2, Thomas
Koop3, Rolf Sander4, William T. Sturges5,
Jonathan P. D. Abbatt6, John T. Jayne7, and Douglas R.
Worsnop7. (1) Institute of Hydrochemistry, Technical University
of Munich, Marchioninistr. 17, Munich D-81377, Germany, Fax:
+49-89-70957999, ulrich.poeschl@ch.tum.de, (2) School of the Environment,
University of Leeds, (3) Physical Chemistry II, University of Bielefeld, (4)
Air Chemistry Department, Max-Planck Institute of Chemistry, (5) School of
Environmental Sciences, University of East Anglia, (6) Lash Miller Chemical
Laboratories, University of Toronto, (7) Aerodyne Research, Inc
Abstract
The traditional ways of scholarly publishing and peer review do not live up
to the needs of efficient communication and quality assurance in today’s
rapidly developing and highly diverse world of science. Substantial
improvement can be achieved by an open access two-stage publication process
with interactive peer review and public discussion. It enables rapid
publication and dissemination of new results in discussion papers followed
by thorough and transparent peer review which is open for input from the
scientific community (permanently archived and fully citable), and it leads
to final revised papers with maximum quality assurance and information
density. This approach has been successfully realized and applied in the
interactive scientific journal Atmospheric Chemistry and Physics (ACP,
www.atmos-chem-phys.org), which is edited by a globally distributed network
of scientists and has been launched in 2001. The achievements of ACP confirm
that the opportunities for interactive peer review and public discussion in
a high quality journal are very much appreciated by authors, referees, and
the scientific community. Reference: U. Pöschl, Interactive journal concept
for improved scientific publishing and quality assurance, Learned
Publishing, 17, 105-113, 2004.
CINF 18: An insider's view of peer review and publishing on the web
Carol Carr, Chemistry Dept. Univ. of PA, Organic Letters, 231 S. 34th
ST, Philadelphia, PA 19104, Fax: 215-573-8256, carrca@sas.upenn.edu
Abstract
Insights on publishing and peer review in the electronic era will be
presented from the perspective of the managing editor of a chemistry
journal, Organic Letters, the first American Chemical Society journal
to accept submissions via the web. These insights are colored by the
editor's previous experience on the consumer side of publishing, as a
chemistry librarian.
CINF 19: Comprehensive sampling of diverse chemistry space: A key
driver for primary screening libraries
Ying Zhang, Jean Patterson, Libing Yu, and Carmen M. Baldino,
Department of Chemistry, ArQule, Inc, 19 Presidential Way, Woburn, MA 01801,
Fax: 781-994-0678, yzhang@arqule.com
Abstract
Diversity-oriented synthesis (DOS) provides an efficient strategy for
accessing an almost infinite amount of diverse chemistry space with complex
and functionally dense natural product-like structures. However, the
challenge of rapidly developing the required chemical methods to synthesize
these high value libraries still remains. Herein, we describe our
standardized chemistry development approach that leverages the systematic
sampling of the desired chemistry space to provide much needed efficiencies.
Application of this strategy has afforded the efficient development of high
throughput chemistry protocols delivering significant collections of
purified screening libraries that embody the desired balance of
physicochemical properties to support early stage drug discovery programs.
CINF 20: Modeling a business process in drug discovery with WebSphere
Business Integration Modeler to assist solutions development
Jean Wang and Jay Zhao, Healthcare and Life Sciences, IBM, Boca
Raton, FL 33487, Fax: 877-209-0085
Abstract
Using a scenario of drug discovery, this paper illustrated how IBM WebSphere
Business Integration (WebSphere BI) Model offerings be used to create
scientific business process models to bring the scientific business process
and solutions development together. WebSphere BI Modeler provides a
collaboration environment where domain experts, process managers, architects
and IT developers share and contribute to the life cycle of solutions design
and development.
CINF 21: MS5 – A general interface to ADME and search results
Matthew J. Walker1, Richard D. Hull2, Suresh B.
Singh3, Robert P. Sheridan1, and J. Christopher
Culberson1. (1) Molecular Systems, Merck Research Laboratories,
126 E. Lincoln Ave., RY50SW-100, Rahway, NJ 07065, Matthew_Walker@Merck.com,
(2) Axontologic, Inc, (3) Concurrent Pharmaceuticals
Abstract
The Pharmaceutical industry is under significant pressure to produce more
and more medicines while at the same time reducing costs to the patient.
This translates to pressure on scientists to decrease the time and expense
of the research and development process. As a result, modelers are
continually looking for new ways to produce and consume information about
chemical entities. To this end the MS5 tool was originally developed to
facilitate structural similarity searching by providing an integrated
environment and a similar look-and-feel to several searching methods. As new
workflows emerged, this tool was expanded and now covers ADME property
lookup and prediction, site of metabolism prediction and Lipinski inspired
filtration. Implementation of the MS5 web tool, as well as prospects for its
future development are herein discussed.
CINF 22: Dealing with the concepts of “chemical compound” vs “chemical
structure”
Robert S. Pearlman, Yubin Wu, Karl M. Smith, and Brian B. Masek,
Optive Research, Inc, 12331-A Riata Trace Parkway -- Suite 110, Austin, TX
78727, bob.pearlman@optive.com
Abstract
Chemical compounds can exist in various protonation states and in various
tautomeric states – two aspects of what shall, henceforth, be referred to as
the "protomeric state" of a compound. Different protomeric states correspond
to different connection tables – hence, different structures – of a
compound. A compound’s environment (solvent, membrane, receptor, etc.)
determines the protomeric state which the compound is most likely to adopt.
Experimentally measured properties reflect Mother Nature’s choice of which
structure(s) predominates and determines the measured property value.
Regrettably, we often tend to forget these facts when generating or
assessing or storing predicted properties of compounds obtained from
calculations based on a particular structure we or some other human chose to
associate with the compound.
We need to be able to enumerate and consider the various structures which a
compound might exhibit in different Natural environments. We need to be able
to associate measured data with compounds while associating computed data
with the particular structures used for the computations. We need a robust
method to associate any given structure with its corresponding, canonically
identified compound. This presentation will introduce algorithms and
software tools which address these needs and others.
CINF 23: Tapping into the InnoCentive global
solver community to obtain innovative solutions for R&D
Poonam Narula, Yi Shi, Peter Lohse, Eugene Ivanov, and Jill Panetta,
InnoCentive Inc, Andover, MA 01810, pnarula@innocentive.com
Abstract
We have developed a global scientific community to provide leading pharma,
chemical and consumer product companies with solutions to their scientific
challenges in chemical and applied sciences. Our communication with
chemistry experts all around the globe is facilitated by the networking
power of the internet. We have developed a secure website which regulates
information and intellectual property transfer. Solution seekers contract
with InnoCentive in order to post scientific questions on InnoCentive.com.
Each scientific challenge includes a detailed description and requirements,
a deadline, and an award amount for the best solution. Scientists worldwide
are eligible to register on the web site as "Solvers" which are currently
from over 150 countries.
This presentation will provide examples of problems posted as challenges in
chemical and applied sciences which have been presented to our solver
community and the power of this forum to provide solutions to the
multinational companies.
CINF 24: Screening molecules for their drug-like
index
Anwar Rayan, Andrea Scaiewicz, Inbal Geva-Dotan, Dinorah Barasch, and
Amiram Goldblum, Department of Medicinal Chemistry and the David R.
Bloom Center for Pharmacy, Hebrew University of Jerusalem, School of
Pharmacy, Jerusalem 91120, Israel, Fax: 972-2-675-8925, anvarr@md.huji.ac.il,
amiram@vms.huji.ac.il
Abstract
A new drug like index (DLI) is presented. It is formed by applying the
Iterative Stochastic Elimination (ISE) algorithm (1-4) for constructing a
set of options to differentiate between drugs and non-drugs (CMC/ACD) with
appropriate training and test sets. The set of best solutions forms the
basis for constructing DLI, as a sum over the relative contributions of true
and false negatives and positives to each of the solutions. The best
k-descriptor combinations out of some 150 descriptors have been picked by
ISE, as well as their optimal limits for differentiating between drugs and
non-drugs. DLI has been applied to several groups of the MDDR database,
resulting in several implications for DLI values of different phases in
clinical trials. The use of DLI for constructing combinatorial libraries
will be demonstrated.
References: (1) Glick et al., PNAS 2002, 99, 703-708. (2) Glick et al.,
Proteins 2000, 38, 273-287. (3) Rayan et al., Curr Med Chem 2004, 11,
675-692. (4) Rayan et al., J Mol Graph Model 2004, 22, 319-333.
CINF 25: A self-organizing algorithm for generating biologically active
conformations
Sergei Izrailev1, Huafeng Xu2, and Dimitris K.
Agrafiotis1. (1) 3-Dimensional Pharmaceuticals, Inc, 8 Clarke
Drive, Cranbury, NJ 08512, (2) Department of Pharmaceutical Chemistry,
University of California San Francisco
Abstract
Conformational sampling of small molecule structures has been a widely used
technique in structure-based drug design and virtual screening. A stochastic
algorithm for conformational sampling is presented. The algorithm generates
molecular conformations that are consistent with a set of geometric
constraints, which include interatomic distance bounds and chiral volumes
derived from the molecular connectivity table. The algorithm repeatedly
selects individual geometric constraints at random and updates the
respective atomic coordinates toward satisfying the chosen constraint. The
ability of the algorithm to generate low-energy and biologically active
conformations is discussed.
CINF 26: Open Access publishing: An overview
Bill Town, Kilmorie Consulting, 24A Elsinore Road, London SE23 2SL,
England, bill.town@kilmorie.com
Abstract
Open Access – free online accessibility of research papers – is already one
of the most heated in the field of scholarly communications and is currently
the focus of a Parliamentary Inquiry in the UK. Open Access can be achieved
in two ways: either author self-, institutional- or subject-based archiving
of papers in parallel with publication in traditional subscription-based
journals, or the conversion of journals themselves to a free-to-access
business model, where costs are covered by payment on behalf of the author
rather than on behalf of the reader. A brief historical overview of
developments in Open Access will be given as an introduction to the two
sessions dedicated to considering aspects of Open Access.
CINF 27: Open Access publishing: The promise and
the reality for libraries
Michael Leach, Physics Research Library, Harvard University, 17
Oxford St., Cambridge, MA 02138, Fax: 617-495-0416, leach@eps.harvard.edu
Abstract
Open Access, as a new publishing model, promises to deliver a number of
advantages for readers and librarians, including little or no cost for
libraries, free access to any interested reader, liberal copyright
agreements and extensive permissions for authors. Some envision Open Access
as the magic bullet that will solve the serials crisis of the past decade.
Certain challenges, though, have arisen already, including the potential
high cost of article page charges, which can hinder adoption by research
communities; the initiation of "support fees" paid by libraries in lieu of
article charges; numerous long-term preservation and archiving issues; and
an untried economic model. Other issues are just beginning to arise: "fiscal
aggregation" of article fees via libraries; implementation of LOCKSS (Lots
Of Copies Keep Stuff Safe) models to enhance persistence of digital
articles; the impact on collection development and technical services in
libraries; and integration with institutional repositories. This
presentation will address these challenges, focusing on the near-future
impact of Open Access publishing on library collections, budgets and
services.
CINF 28: How Open Access will affect the small
society publisher
Sarah Cooney, Society of Chemical Industry, 15 Belgrave Square,
London SW1X 8PS, United Kingdom, Fax: +44 (0)20 7235 0887, sarah.cooney@soci.org
Abstract
SCI is a unique international forum where science meets business on
independent impartial ground. Members include consumer representatives,
environmentalists, industrialists and academic researchers, and the Society
offers a chance to share information between sectors as diverse as food and
agriculture, pharmaceuticals, biotechnology and chemicals. Founded in London
in 1881, today SCI is a registered charity with members in more than 70
countries. SCI’s charter requires that the Society shall “advance …science
for public benefit by…publishing appropriate journals, books and other
communications”. SCI is a small publisher, owning 4 peer-reviewed journals
that are well-respected niche titles (Journal of the Science of Food &
Agriculture is ranked second in its field category). Journals provide a
large proportion of the Society’s gross revenue to SCI; the surplus (after
funding associated editorial and other services) is invested back into the
society. This surplus is vital for funding a range of educational
activities, awards and bursaries both in the developed and developing world.
This talk will explore some of the issues that face small societies like SCI
in the light of the Open Access movement.
CINF 29: Open Access and scholarly publishing
Peter S Gregory and Robert Parker, Royal Society of Chemistry, Thomas
Graham House, Science Park, Milton Road, CB4 0WF Cambridge, United Kingdom,
gregoryp@rsc.org
Abstract
Regular science publishing started with the Royal Society's Philosophical
Transactions nearly 400 years ago. Today, many of the world's leading
scientific societies have publishing operations and many of the best known
science journals are published by societies. Societies have a commitment to
the dissemination of science, the maintenance of ethical and scientific
standards, and the need to guarantee the scientific record, but many
societies also rely on the surpluses generated by their publishing
operations to fund these and other charitable activities. Do open-access
models provide a boost to the activities of societies or do they gnaw away
at the very fibre of science?
CINF 30: Open Access: Early stages of clinical
trials
Robert D. Bovenschulte, American Chemical Society Publications
Division, 1155 16th Street NW, Washington, DC 20036, Fax: (202) 872-6060,
rbovenschulte@acs.org
Abstract
While open access has many definitions, the central meaning is that anyone
can have free online access to any scientific or other research-based
information, particularly the most up-to-date content of technical journals
on the Web. Proponents of open access tout its benefits and advantages over
the established subscription model for scholarly publishing. Less often,
however, do they examine the various assumptions, concerns, issues, and
ramifications that a shift to this new model may entail. This presentation,
in a spirit of objectivity, will review the promise of open access and the
obstacles that it must overcome to be successful. The presentation will also
consider the possibility of unintended and deleterious consequences that may
ensue if open access becomes dominant. The message being advanced here is
that open access, like a new pharmaceutical drug, should be thoroughly
tested in an analog to clinical trials before it is widely adopted. A
limited and protracted experiment will allow the scholarly community to
determine whether open access can be effective and salutary for scientific
communication and publishing.
CINF 31: Elsevier: A commercial publisher's
perspectives on Open Access
Karen Hunter, Elsevier, 360 Park Avenue South, New York, NY 10010,
k.hunter@elsevier.com
Abstract
The publishing industry, academia, and scientific research itself, have gone
through a tidalwave of change since the emergence of the internet. During
the early days of the transition to online publishing, many perceived a
revolution of science in the making. Today, usage of scientific journals
online has doubled year on year, indicating that scientific information is
reaching users like never before. At the same time, library budgets continue
to be reduced and libraries are forced to make difficult decisions about
collection development and access. Various forms of "pay to publish" models
are surfacing, as well as alternative distribution models. Now once again,
revolution is in the air. This presentation will include proprietary
Elsevier research and focus on Elsevier's view, as a commercial publisher,
on Open Access and related activities, such as Open Archiving and
institutional repositories, as well as the general outlook for the future.
CINF 32: The gold and the green roads to Open
Access
Stevan Harnad, Canada Research Chair, Universite du Quebec a
Montreal, Montreal, QC H3C 3P8, Canada, Fax: 514-987-8952, harnad@uqam.ca
Abstract
Open Access (OA) is
optimal and inevitable for the research community because it maximises
research usage and impact, hence also progress and productivity. There are
two roads to OA, however, and Open Access Journal Publishing, the
"golden road," is only one of them, and
neither the fastest nor the surest, because its cost-recovery model has
not yet been tested enough for sustainability and because it would take a
long time to convert
24,000 peer-reviewed journals into OA Journals. (Only
about 1000 of them, <5%, are OA so far.) The green road to OA is to
continue publishing in non-OA journals when there is no suitable gold
journal, but to self-archive
one's articles in one's own OAI-compliant
institutional Eprint Archive.
Over
80% of journals have already given their green light to author
self-archiving, but self-archiving is still
far from using its full potential to provide immediate OA. What are
needed are empirical demonstrations of the dramatic
causal effect of OA on citation impact along with a formal extension of
universities' existing publish-or-perish policies to include
providing OA for all the university's refereed research article putput.
CINF 33: DSpace as an institutional repository
Erja Kajosalo and Margret Branschofsky, MIT Libraries, Massachusetts
Institute of Technology, 14S-M48, 77 Massachusetts Ave, Cambridge, MA
02139-4307, Fax: 617-253-6365, kajosalo@mit.edu
Abstract
DSpace is an open source software platform that enables the establishment of
institutional repositories for digital collections of academic research and
educational material. It provides for the capture, description, distribution
and preservation of digital materials of various formats. This presentation
will briefly describe the benefits of an institutional repository, how the
DSpace functionality supports these ideas, as well as emerging policy
issues, such as user education, intellectual property, and faculty response.
Worldwide implementation of the DSpace software and the future of the DSpace
federation will be discussed.
CINF 34: Citation impact of Open Access journals
Marie E. McVeigh, Product Development Manager, Thomson-ISI, 3501
Market Street, Philadelphia, PA 19104, Fax: 215-387-4706, marie.mcveigh@thomson.com,
and James Testa, Director, Editorial Development, Thomson Scientific
Abstract
Open Access (OA) represents one of the most significant changes to
scientific publishing in recent years. But has Open Access fundamentally
changed the dynamics of scholarly citation? We have studied the citation
behavior of OA journals compared to journals of similar size and scope that
maintain a traditional subscription model. Year 2002 data on 191 OA journals
in the ISI citation databases suggest that offering unrestricted access to
journal contents on the web does not, itself, ensure higher citation
activity to the journal. We will present data from the year 2003 Journal
Citation Reports™, comparing journal citation metrics between OA and non-OA
publications. A particular focus will be placed on Chemistry journals, with
several aspects of their citation dynamics examined in detail.
CINF 35: Scholarly communication in the digital
environment: Chemistry and chemical engineering
Ian Rowlands, Department of Information Science, City University
London, Centre for Information Behaviour and the Evaluation of Research (CIBER),
Northampton Square, London EC1V 0HB, United Kingdom, Fax: +44 (0207) 040
8584, ir@soi.city.ac.uk
Abstract
This paper will present the key findings of an international survey of
senior journal authors carried out by ciber, in association with the UK
Publishers' Association and NOP, in early 2004. Responses were received from
nearly 4,000 corresponding authors, making this possibly the largest survey
of author attitudes to open access and other publishing initiatives so far.
The main findings reveal a surprising lack of knowledge of open access: 82%
of authors claimed to know 'nothing' or 'just a little' about this movement.
Authors' general reluctance to contribute towards the costs of commercial
open publishing (can't pay, won't) is severe and probably no where near the
level required for sustainable commercial services. The paper contrasts
these general findings with those obtained in the fields of chemistry and
chemical engineering.
CINF 36: Open Access: Medium and long term
implications for academic libraries
David Goodman, Palmer School in Manhattan, New York University, Bobst
Library, Room 707, 70 Washington Square South, New York, NY 10012-1379, Fax:
212-995-4072, dgoodman@liu.edu
Abstract
Academic librarians usually agree about a single aspect of journal articles
in chemistry and other sciences: there is one system which is not viable in
the long run--the presen t system. There is less agreement about remedies.
There are many potential candidate systems but very little experience,
especially about long-term viability and compatibility. Those committed to
any of the alternatives can construct strong arguments, but in the absence
of reliable theory or sufficient experiment, we are left with opinion--and
prejudice. This talk shall summarize what I regard as the range of plausible
future prospects, with mention of the views of those who see it differently.
CINF 37: Cheminformatics' role in the
pharmaceutical industry
Randal Chen, Abbott Laboratories, 100 Abbott Park Road, Dept. R42T,
Building AP10-2, Abbott Park, IL 60064, randal.chen@abbott.com
Abstract
The productivity gap in the pharmaceutical industry is typified by the
statistic that only 10% of the compounds that enter into development, will
make it to the market place. Many factors determine success or failure, but
a key and common strategy of the industry is to effectively employ
computational methods, such as cheminformatics, to enhance the odds of
success. The presentation will cover: 1) Key technological issues – what
cheminformatics technologies are currently emphasized. 2) Technological
framing of the problems – what types of questions the industry needs to
answer. 3) Types of individuals and skill sets need to tackle these problems
– what background and training emphasis should schools provide their
students. 4) Organizational models and structures influence – how
organizational factors impact an employer’s approach a problem (such as
size, culture, financial state) and how that affects the role.
CINF 38: Masters level training in
chem(o)informatics in the UK
Peter Willett, Department of Information Studies, University of
Sheffield, Western Bank, Sheffield S10 2TN, United Kingdom, p.willett@sheffield.ac.uk,
and Helen Cooke, GlaxoSmithKline, 709 Swedeland Road, King of
Prussia, PA 19406, helen.2.cooke@gsk.com
Abstract
In the late 1990s the Engineering and Physical Sciences Research Council (EPSRC)
in the UK began to seek proposals for funding for development of Masters
Training Package (MTP) courses in areas where a shortage of suitably
qualified graduates was perceived. One area identified was cheminformatics,
and both the Department of Information Studies at the University of
Sheffield and the Chemistry Department at the University of Manchester
Institute of Science and Technology (UMIST) were awarded funding for a
five-year period. While both courses embrace the MTP philosophy of engaging
industry and exploring new delivery methods to assist the sustainability of
the courses, they have their individual “flavours”, reflecting the differing
research and teaching interests in the respective departments. This
presentation examines the content and evolution of the courses and reports
on the careers of some of the students, attitudes of industry and future
prospects.
CINF 39: Chemical informatics and bioinformatics
programs at Indiana University
Gary D. Wiggins, School of Informatics, Indiana University, 901 East
Tenth Street, Bloomington, IN 47408-3912, Fax: (812) 856-4764, wiggins@indiana.edu
Abstract
The graduate program of instruction in informatics at Indiana University
includes paths to an MS degree in bioinformatics and chemical informatics.
The latter has a specialized track on the Indianapolis campus in laboratory
informatics. In existence only since 1999, the IU School of Informatics
trains students in the application of computer science to various
disciplines. The programs will be described and plans for a PhD program in
science informatics, to be implemented in the fall of 2005, will be
outlined.
CINF 40: Advances in enterprise-wide management
of spectral data
Marie Scandone1, Gregory M. Banik2, Deborah
Kernan3, and Victoria Rafalovsky2. (1) Informatics
Division, Bio-Rad Laboratories, Inc, 3316 Spring Garden Street,
Philadelphia, PA 19104, Fax: 215-662-0585, marie_scandone@bio-rad.com, (2)
Bio-Rad Laboratories, Informatics Division, (3) Informatics Division, Bio-Rad
Laboratories
Abstract
Proper management of a proprietary data is complex, yet crucial. In the
pharmaceutical, chemical, and petrochemical industries, samples are
typically analyzed and characterized using multiple techniques including,
but not limited to IR, NMR, UV/Vis, GC, MS, Raman, and NIR. As an added
complication to the problem of organizing multi-technique data, data within
a given technique may be taken from instruments supplied by more than one
vendor. The result is a complex matrix of data types and vendor formats.
Organizations are faced with the problem of storing and serving this data
are faced with overlapping issues involving data cross-referencing, data
reporting, correlation with structure and property information, user
training, and software control & management.
This paper will discuss these challenges and describe a solution to
integrate data types; search, retrieve, and analyze the data; and
consequently communicate information to colleagues via sophisticated
reporting features.
CINF 41: AQUIRE: ArQule's united repository and information exchange
system
Rojnuckarin Atipat and Sergio H. Rotstein, ArQule, Inc, 19
Presidential Way, Woburn, MA 01801, Fax: 781-376-6019, arojnuckarin@arqule.com
Abstract
The informatics infrastructure at ArQule consists of a set of highly
specialized scientific database systems and a central information repository
that unifies the distributed information. The central repository is ArQule's
United Repository and Information Exchange (AQUIRE) system, which integrates
the data from array production, reagent procurement and inventory,
analytical and biological database systems. It gives our scientists the
ability to query and report on data spanning multiple systems from a single
application. Automatic propagation of data ensures that information (e.g.
plates, compounds), entered in one system will also be available in the
other systems. A role-based security scheme allows the system to enforce any
necessary data access restrictions
CINF 42: Molecular docking using ArgusLab: An efficient shape-based
search algorithm and an enhanced XScore scoring function
Mark A. Thompson, Planaria Software, Seattle, WA 98155, mark@planaria-software.com
Abstract
We have developed an efficient grid-based docking method in ArgusLab that
approximates an exhaustive search. We employ a simple geometric fit of a
flexible ligand in the binding site at carefully-chosen search points within
the free volume of the binding site cavity, along with incremental
construction of the ligand’s torsions in a breadth-first order that
maximizes the early rejection of unproductive pose fragments and greatly
enhances the efficiency of the conformational search. We have coupled this
with a simple scoring function, based on an enhancement of the XScore(HP)
method of Wang and coworkers. Our enhancements allow the scoring function to
be used as the objective function during docking and to include waters found
in the X-Ray structure. Using the 100-target/100-pose sets of Wang et. al.,
we obtain 80% agreement of the lowest scoring pose being within 2.5 Angstrom
RMSD of the X-Ray structure, and a correlation coefficient of 0.61 between
binding scores and experimentally determined binding affinities. Typical
docking times for ligands with 10-20 torsions are 30-90 seconds on a 2.4 GHz
laptop computer. The 1cbx/benzylsuccinate structure (5 ligand torsions)
docks in less than 10 seconds, which is typical for systems of this size.
ArgusLab’s docking method is implemented for both interactive and virtual
high-throughput screening of ligand databases. Simplicity in the sample
preparation is stressed in our design as well as a configurable parameter
set for the scoring function that allows the user to select modified
parameters at runtime. ArgusLab implements a rich graphical presentation of
the results of a docking calculation, including easy navigation between the
poses in the final set located in the search (typically, the 50 lowest
energy poses are retained for analysis).
CINF 43: Write new books or buy/translate famous books in developing
countries?
Stefan Perisanu, Laboratory of General Chemistry, Polytechnic
University of Bucharest, 1 Polizu str, Bucharest 78126, Romania, Fax:
40-21-3111796, s_perisanu@chim.upb.ro
Abstract
In developing countries, like Romania, universities do not have enough money
to buy the best books and especially not enough copies, in order to provide
the students the necessary documentation. Given this situation most
professors write their own book for each course. Although many good books
were written in my country (some of them are appreciated even by students
studying in western countries) alternative sources of information are more
than necessary, not only for students, but also for teachers. A different
selection of information, a more up-to-date information, or a more
appropriate pedagogical approach are some of the reasons of this need. Some
solutions to this problem are envisaged : copyright transfer and/or free
Internet access to some classical textbooks, documentation stages for
students and professors, co-operation between libraries. A discussion, in
order to find the best alternative(s) is desired, by the author.
CINF 44: Development of protein moment descriptors and pH-dependent
descriptors for prediction of protein affinity in hydrophobic interaction
chromatography systems
Qiong Luo1, Asif Ladiwala2, Dechuan Zhuang1,
N Sukumar1, Curt M Breneman1, and Steve M.
Cramer2. (1) Department of Chemistry, Rensselaer Polytechnic
Institute, Cogswell 306, 110 8th St, Troy, NY 12180, Fax: 518 276-4045, luoq@rpi.edu,
brenec@rpi.edu, (2) Department of Chemical and Biological Engineering,
Rensselaer Polytechnic Institute
Abstract
Hydrophobic Interaction Chromatography (HIC) is commonly employed in the
biotech industry for the downstream processing of proteins and other
biomolecules. The selectivity of this technique can be optimized by varying
the composition of the stationary phase as well as the pH of the mobile
phase. In the present work, the effect of resin chemistry on binding
affinity of proteins in HIC are investigated using high-throughput
experimentation and Quantitative Structure-Retention Relationship (QSRR)
modeling. Linear gradient experiments were carried out for 36 proteins on
four different HIC resins having different backbone and ligand chemistries
¨C namely Phenyl Sepharose, Butyl Sepharose, Phenyl 650M and Butyl 650M. A
number of sets of novel protein descriptors are developed in this study,
including moment descriptors and pH-dependent descriptors, which are based
on RECON/TAE method and MOE descriptors. In the development of protein
moment descriptors, moments of various physico-chemical property
distributions of proteins up to and including second order are calculated
based on protein crystal structures using either all the protein atoms or
only surface atoms identified by Delaunay Tessellation. Restricting the
descriptors to surface atoms eliminates the contributions of atoms on deeply
buried residues. Support Vector Machine (SVM) regression has been employed
to obtain predictive QSRR models. The predictive ability of these models are
verified for a randomly selected test set of proteins not included in the
training of the model. The relative importance of each selected descriptor
in the final models are provided by star plot analysis and correlation
matrices. Once these predictive models have been validated, they can be used
as an automated prediction tool for Virtual High-Throughput Screening (VHTS).
CINF 45: Building classification models for DMSO solubility: Comparison
of five methods
Jing Lu and Gregory A. Bakken, Scientific Computing Group, Groton
Computational Chemistry, Pfizer Global R&D - Groton Labs, Eastern Point
Road, Groton, CT 06340, Fax: (860) 7153149, jing.j.lu@pfizer.com
Abstract
It is now increasingly recognized that DMSO solubility is a problem at least
as serious as compound stability in combinatorial libraries, since it may
cause artifacts in library screening, and thereby negatively impact
screening efficiency. It is desirable to have an effective in silico model
for estimation of DMSO solubility to reveal any poorly soluble compounds,
which are incompatible with assay protocols prior to screening runs. In this
study DMSO solubility data at 30 mMol were gathered for 33,329 Pfizer
compounds. Five linear and nonlinear classification methods were evaluated
and compared on the data set using a set of 200 2D descriptors. Five
predictive binary classification models for estimation of DMSO solubility
class of organic compounds were derived and validated. The results show the
high accuracy using ensembles of decision trees (specifically, boosting and
random forests). Additionally, methods like LDA and BinaryQSAR, when used in
conjunction with feature selection methods, provide accurate models. While
not quantitative in nature, models such as these are effective for screening
compounds to be stored in DMSO for potential solubility problems.
CINF 46: Docking studies on hERG model
Anna Maria Capelli1, Aldo Feriani2, Frank E
Blaney3, Diego Dal Ben1, Giovanna Tedesco1,
and Alfonso Pozzan4. (1) Computational, Analytical and Structural
Sciences, GlaxoSmithKline, Medicines Research Centre Via Alessandro, Fleming
4 37135, Verona, Italy, Fax: +39 0459218196, Anna-Maria.M.Capelli@gsk.com,
(2) GlaxoSmithKline Research Centre, (3) Computational, Analytical &
Structural Studies, GlaxoSmithKline, (4) Chemistry Department, Computational
Chemistry and Compound Diversity Unit, Verona Research Centre, Glaxo Smith
Kline S.p.A
Abstract
Drug-induced QT interval prolongation, which is a major risk for torsades de
pointes arrhytmia, can be related to the inhibition of the K+ channel
encoding by human ether –a –go-go related gene (HERG). As a consequence,
evaluation of potential pharmacological liability associated to hERG is an
important aspect of the drug discovery process. In this study, docking
experiments in an in house hERG receptor model were performed to study a set
of hERG standards. Validation of the poses obtained was then performed using
site-directed mutagenesis experiments reported in the literature and the
affinity of the ligands correlated with empirical scoring functions. The
method was then used to perform docking experiments of in house ligands and
used to drive drug design activities.
CINF 47: LCOLI -- efficient generation of diverse combinatorial
libraries
Rong Chen and Alan Long, Department of Chemistry and Chemical
Biology, Harvard University, 12 Oxford St., Cambridge, MA 02138, chen@lhasa.harvard.edu,
aklong@fas.harvard.edu
Abstract
The program LCOLI (an acronym for LHASA for Compound Libraries) is a new
module for the LHASA (Logic and Heuristics Applied to Synthetic Analysis)
suite that predicts possible reactions between input starting materials and
generates virtual combinatorial libraries. The libraries created using this
knowledge based diversity-oriented synthesis (DOS) approach achieve a high
degree of chemical diversity and complexity, rich information on synthetic
accessibility, and predictions of potential toxicity. Library generation is
highly efficient and holds great promise for new drug discovery. Samples of
analyses will be presented.
CINF 48: Science literacy and information literacy in a middle school
Jennifer E. Lewis1, Troy D. Sadler2, Teresa
Eckart1, and Katherine M. Whitley3. (1) Department of
Chemistry, University of South Florida, 4202 E. Fowler Ave SCA400, Tampa, FL
33620-5250, Fax: 813-974-3203, jlewis@chuma1.cas.usf.edu, (2) School of
Education, Indiana University, (3) Tampa Library, University of South
Florida
Abstract
Chemistry literacy and information literacy were integrated in a project
involving University of South Florida faculty, graduate students and a local
community middle school. The project was a pilot plan for enhancing science
and information literacy in middle school students along with their
families. The project introduced students and their families to the use of
scientific information to make decisions about a socioscientific
issue--namely, global warming. In addition to seeking and evaluating
scientific information pertinent to the issue, students and parents
performed laboratory activities investigating the properties of gases. The
pilot was successful; interviews revealed that both parents and students
valued the experience and that the activities were seen as an integrated
whole. Additional study is required to assess the effectiveness of the
activities within the project, specifically with regard to the integration
of subject-specific science literacy and information literacy.
CINF 49: Dock odysseys. I. The creation of 3D searchable small molecule
databases with consideration of molecular chirality
Zengjian Hu and William M. Southerland, Department of Biochemistry
and Molecular Biology, Howard University College of Medicine and the Howard
University Drug Discovery Unit, 520 West Street, Northwest, Room 324,
Washington, DC 20059, zhu@howard.edu
Abstract
High-throughput docking (HTD) is an important source of new leads in the
drug discovery process. The quality of HTD generated lead compounds are
limited by the chemical database used to generate the candidate molecules.
In addition to structural diversity, molecular chirality should be
considered when creating a 3D searchable chemical database. The
consideration of molecular chirality is an intuitive and simple, but
valuable, approach to improving the quality of chemical databases as well as
HTD, since molecular chirality has a major influence on the pharmacological,
pharmacokinetic, and toxicological actions of therapeutic agents. As far as
we know, although there is rapid growth of public, commercial, and
proprietary small-molecule databases available for HTD, there are no
published reports on the investigation and creation of chiral chemical
databases until now. In this reports, we present for the first time the
creation of 3D searchable small molecule databases with the consideration of
molecular chirality (*This work is supported by grant RCMI-NIH 2G12RR03048).
CINF 50: Dock odysseys. II. The evaluation of AutoDock program and its
comparison with other docking programs
Zengjian Hu1, Shaomeng Wang2, and William M.
Southerland1. (1) Department of Biochemistry and Molecular
Biology, Howard University College of Medicine and the Howard University
Drug Discovery Unit, 520 West Street, Northwest, Room 324, Washington, DC
20059, zhu@howard.edu, (2) Intel Med, The University of Michigan
Abstract
In recent years, computational high-throughput docking (HTD) has emerged as
a very powerful tool for identifying novel lead compounds. In principle, HTD
should discover all of the ligands of interest in a database, but in
practice, HTD suffers from false positives and false negatives. In this
study, we evaluated the AutoDock program for its quality and accuracy in
identifying and predicting ligand binding modes. AutoDock is one of the most
widely used docking programs in computational binding studies. Our results
show that AutoDock is able to predict preotein-ligand complex structures
with reasonable accuracy and speed. We also compared AutoDock program with
three other popular used programs, DOCK, FlexX and GOLD. We found its
performance batter than these three programs. Its use in HTD should enhance
efficiency in the discovery of lead compounds (* This work is supported in
part by grant RCMI-NIH 2G12RR03048).
CINF 51: Separation and determination of urea and methyl carbamate by
reversed phase high performance liquid chromatography
Fulin Mao, Tinghua` Wu, Ya Liu, Zhuoqun Zheng,
Qineng Zhang, and Fei Chen, Insitute of Physical Chemistry ,Zhejiang
Normal University, Jinhua 321004, China, Fax: 086-579-2282595, mflchina@163.com,
wth3907@163.com, sky48@mail.zjnu.net.cn, zhengzhuoqun1980@yahoo.com,
zpy22@163.com, xinyue9877@163.com
Abstract
The method of reverse phase high performance liquid chromatography (RP-HPLC)
was employed in the separation and determination of urea and methyl
carbamate. In order to separate urea from methyl carbamate, two C18 columns
connected in series rather than single one were used. The experiment with
the mobile phase in the proportion of V (methanol): V (water) = 1:1, a flow
rate of 0.5ml/min and volume of feeding of 5µL.. The two components were
quantified by external standard method at the wavelength of 215nm. Under the
optimum conditions listed above, the graph between peak area (A) versus mass
percentage (X%) was linear, with the linear regression equation of urea A =
148565X-39384, R2 = 0.9995 and that of MC A = 69055X-90493, R2 = 0.9985.
Therefore, it may be advisable to apply it to the analysis of the synthesis
of methyl carbamate by alcoholysis of urea.
CINF 52: From synthesis planning to combinatorial
chemistry – applications of the LHASA suite
Alan Long1, Rong Chen2, Craig A. Marby2,
Alexander P. Sukharevsky3, and Keith Ohm2. (1) Harvard
University, 1414 Massachusetts Ave., Room 430, Cambridge, MA 02138, aklong@fas.harvard.edu,
(2) Department of Chemistry and Chemical Biology, Harvard University, (3)
Aventis Pharmaceuticals
Abstract
The LHASA (Logic and Heuristics Applied to Synthetic Analysis) program for
target-oriented retrosynthetic analysis has evolved since the early 1970’s
into a suite of programs that includes DEREK (for toxicology prediction),
PROTECT (for protective-group analysis), APSO (for teaching organic
synthesis), and, most recently, LCOLI (for diversity-oriented generation of
compound libraries). Improvements in hardware and software have shifted the
emphasis in synthetic analysis from interactive, user-driven strategy and
tactic selection to non-interactive processing requiring intelligent
screening of results. One approach to optimal route selection using analysis
of synthetic accessibility and complexity will be discussed. The
availability of multiple tools in the suite also allows a more comprehensive
approach to synthesis planning. For example, the virtual libraries generated
by LCOLI using its knowledge-based diversity-oriented synthesis (DOS)
approach can be screened automatically and ranked according to synthetic
accessibility and potential toxicity of the products. Applications to drug
design will be discussed.
CINF 53: Models for computer reasoning under
uncertainty
Philip N. Judson, LHASA Ltd, Department of Chemistry, University of
Leeds, Leeds LS2 9JT, United Kingdom, Fax: +44 (0) 113 343 6535, judson@dircon.co.uk
Abstract
Human decision makers appear to reach their conclusions through reasoning
based on weighing the arguments for and against propositions. In spite of
their fallibilities, humans perform well enough by this means for
evolutionary success and so their methods deserve consideration as models
for computer reasoning. Bulding on earlier work on the logic of
argumentation, at LHASA we have developed models for reasoning about the
likelihood that an event or circumstance will come about and about whether
some events are more or less likely than others. This talk will outline the
background to our work and present some of the key features of the models we
have developed. We use them in programs for predicting toxicity and
xenobiotic metabolism but they are suitable for any area where predictions
have to be based on uncertain information.
CINF 54: Electronic documents in chemistry, from ChemDraw 1.0 to
present
Stewart D. Rubenstein, CambridgeSoft Corp, 100 CambridgePark Dr,
Cambridge, MA 02140, Fax: 617-588-9380, srubenstein@cambridgesoft.com
Abstract
Although graphical user interfaces had been used for a number of years, the
development of the Macintosh and the laser printer in the mid-80's made it
possible to develop ChemDraw and other programs which became widely
available to non-specialist chemists. More recently, the deployment of
high-speed wide-area networks has made possible global sharing of electronic
documents and other information. This talk will trace the history of some of
these developments, and discuss opportunities today for deeper collaboration
through the use of secure, scalable, global information systems now
available.
CINF 55: A novel method for optimizing subgraph isomorphism algorithms
such that 2D stereochemical descriptors are efficiently processed in a
molecule or reaction retrieval system
Anthony P Cook1, A Peter Johnson1, and Daniel G
Thomas2. (1) School of Chemistry, University of Leeds, Leeds LS2
9JT, United Kingdom, Fax: 44 113 3436465, tony@bci.gb.com, (2) BCI Ltd
Abstract
Subgraph isomorphism algorithms are an essential part of molecule and
reaction retrieval systems. As well as solving queries that express
molecular constitution, an additional requirement is that the absolute or
relative configuration of stereocentres expressed in the query must also be
considered when determining a graph match. In the algorithms we present in
this paper, this problem has been addressed in three ways: a) the
development of a useful and generic stereochemical descriptor that
simplifies the comparison of most types of stereochemical geometry; b) the
incorporation of the comparison of the stereochemical descriptor step
directly into the graph isomorphism algorithm; c) a new feature that uses a
“best first” planning algorithm that dynamically determines the most
efficient order that query atoms and stereo descriptors are tried in the
subgraph isomorphism algorithm.
CINF 56: Strategies and challenges in predictive
toxicology
Glenn J. Myatt, Paul E. Blower, Kevin P. Cross, Wayne P. Johnson, and
Chihae Yang, Leadscope, Inc, 1393 Dublin Road, Columbus, OH 43215, Fax: 614
675 3732, gmyatt@leadscope.com
Abstract
There are numerous challenges to the development of a comprehensive strategy
for predictive toxicology. Access to high quality data from which accurate
predictive models can be generated, continues to be a major impediment. An
approach to domain-intelligent integration of disparate sources, both
electronic and non-electronic, will be described. A toxicology controlled
vocabulary, ToxML, based on the XML standard is central to the integration.
Prior to building any predictive model, an assessment of the data is
required to transform complex hierarchical XML data into decision point
data. This process usually involves an expert judgment. Only once the data
has been selected, integrated and assessed can model building start and even
then there is no guarantee that the data can be modeled. An approach to
building and applying predictive model will be described from various stages
of the workflow, the data integration, assessment, and subsetting to prepare
modelable data set.
CINF 57: Virtual screening and similarity
searching using binary kernel discrimination
Peter Willett, Department of Information Studies, University of
Sheffield, Western Bank, S10 2TN Sheffield, United Kingdom, Fax:
+44-114-2780300, p.willett@sheffield.ac.uk
Abstract
Binary kernel discrimination (BKD) is a machine learning technique that has
recently been suggested for use in virtual screening. A molecule is scored
by calculating its similarities with sets of known active and known inactive
molecules, the number of these similarities contributing to the overall
score for that molecule being determined by an optimisable parameter. This
paper reports the use of BKD in simulated virtual screening experiments with
public and corporate datasets in which the molecules are characterised by 2D
fragment bit-strings. Our results suggest that BKD is fully competitive with
existing approaches to 2D virtual screening in terms of its ability to
prioritise compounds for biological testing. We also demonstrate that a
simple modification of the method provides an effective way of carrying out
similarity searches when multiple reference structures are available.
CINF 58: Virtual screening using reduced graphs
Valerie J. Gillet, Information Studies, University of Sheffield,
Regent Court, 211 Portobello Street, Sheffield S1 4DP, United Kingdom, Fax:
+11 (0) 114 2780 300, v.gillet@sheffield.ac.uk
Abstract
Many different ligand-based virtual screening methods have been developed
using both 2D and 3D descriptors. Both types of descriptors have their
limitations. The 2D methods have a tendency to select structural analogues
and thus do not easily permit the identification of new lead series. The 3D
methods, on the other hand, have been shown to result in greater diversity
in the hitlists, however, they are limited by the need to handle
conformational flexibility. We have developed virtual screening methods in
which the molecules are characterised by reduced graphs which summarise the
features of the molecules while retaining the topology between the features.
Thus reduced graphs can be thought of as topological pharmacophores. Two
different approaches have been investigated for quantifying the similarity
of reduced graphs. In one approach, the reduced graphs are mapped to
fingerprints before calculating the similarity, in the other, graph-matching
methods are applied directly to the reduced graphs. Here, the performance of
the reduced graphs is compared with conventional descriptors in simulated
screening experiments.
CINF 59: Conformational sampling in a protein-ligand complex
environment
Zsolt Zsoldos, Research and Development, SimBioSys Inc, 135 Queen's
Plate Dr, Suite 520, Toronto, ON M9W 6V1, Canada, Fax: 416-741-5084, zsolt@simbiosys.ca
Abstract
Adequate conformational sampling of small molecule ligands is of high
importance in flexible ligand docking as well as in de novo ligand design
applications. There are software tools available to generate low energy
conformers of ligands, i.e. distinct local minima of the conformational
strain energy function of the ligand. Docking and de novo design software
often use such sets of conformers or generate them on the fly by use of
dihedral angles normally associated with low energy conformers.
Conformational statistics of over 5000 high resolution (less than 2.5A)
crystal structure complexes from the PDB will be presented. The experimental
data demonstrates much wider conformational variation in a protein-ligand
complex environment. Requirements are derived from the data for the
necessary conformational sampling space and resolution to reproduce the
experimental data within acceptable bounds for steric violations. The
efficiency of various algorithms to provide the adequate conformational
sampling will be compared.
CINF 60: Informatics aiding drug discovery - ADME evaluation
William L. Jorgensen, Department of Chemistry, Yale University, New
Haven, CT 06520-8107, Fax: 203-432-6299, william.jorgensen@yale.edu
Abstract
Computational tools have been developed for the rapid prediction of
properties of organic molecules that are relevant to their potential as
drugs. A small number of physically significant descriptors, especially
surface area components and hydrogen-bonding potentials, are computed from
an input three-dimensional structure. Simple linear regression equations
have been developed from experimental datasets using these descriptors for
the accurate prediction of a variety of properties including aqueous
solubility, octanol/water partition coefficient, free energy of hydration,
Caco-2 and MDCK cell permeabilities, serum protein binding, and brain/blood
partitioning. Other developments include a rule-based system for prediction
of primary metabolites, while a more quantitative approach has been used in
the computation of pKa values (acidities). The algoritms have formed the
basis of the QikProp program.
Prediction of Drug Solubility from Structure. W. L. Jorgensen and E. M.
Duffy, Adv. Drug Delivery Reviews, 54, 355-366 (2002).
CINF 61: A role for chemoinformatics in structure-based de novo
ligand design
A. Peter Johnson, Krisztina Boda, Tamas Lengyel, Shane Weaver, and
Aniko Vigh, School of Chemistry, University of Leeds, Leeds LS2 9JT, United
Kingdom, Fax: 44-113-2336465, a.p.johnson@chemistry.leeds.ac.uk
Abstract
The SPROUT program for de novo ligand design benefits from extensive use
made of chemical information extracted from a variety of databases and
knowledge bases. Databases of x-ray structures such as CSD and the
Brookhaven file provide support for the generation of conformations which
should be of relatively low energy because they correspond to ones
frequently found in these databases. Supplier catalogues, combined with
retrosynthetic fragmentation of MDDR provide starting materials for the
SynSPROUT variation in which structures are built up by virtual synthesis
using common synthetic reactions stored in a reaction knowledge base. An
alternative fragmentation of MDDR provides drug like entities which are
flood docked to all possible target sites in a protein cavity. Analysis of
the estimated binding affinity scores for all poses allows an informed
choice of a subset of target sites for further structure generation.
CINF 62: Chemical information instruction in an industrial environment
Catherine Lyons Misner, Rohm and Haas Company, 727 Norristown Road,
P.O. Box 0904, Spring House, PA 19477-0904, Fax: 215 – 641 – 7811, cmisner@rohmhaas.com
Abstract
The need for chemical information and awareness of new resources grows
exponentially for research chemists and (chemical) engineers who move from
the academic to the industrial arena. Continuing effective instruction in
retrieving and evaluating available chemical and engineering information can
be a challenge to the Corporate information professional. This poster will
address the issues we in the Knowledge Center face, and will outline some
solutions we at Rohm and Haas Company are employing to meet the challenge.
Industrial sector scientists are constrained by the time they can devote to
the amount of available data and information. We have determined a key
factor in effective use of the plethora of resources we teach, is the manner
in which we present our training sessions and materials. The focus of our
instruction has migrated from “here’s what we have” to “here’s what you will
get” out of the resource or “here’s what you can do” with an information
resource. We run training sessions to enable scientists to create their own
accelerated information analyses (in a kilosecond). Our presentations have
to address wide ranges in educational levels and computer skills, as well as
an increasingly global audience. We will describe how we leverage existing
technology in overcoming some of these obstacles. We have created quick
reference guides linked from our web page, and collaborated with vendors to
translate presentations into other languages. We are creating brief, focused
online tutorials, and we use collaboration tools (like Sametime™ or WebEx™)
for providing training to remote locations. We attempt to balance our
charter to provide appropriate information to our customers via self-service
with our role as highly trained consultants and partners.
CINF 63: Information literacy for the physical scientist
Leah R. Solla, Physical Sciences Library, Cornell University, 293
Clark Library, Cornell University, Ithaca, NY 14853-2501, Fax: 607-255-5288,
lrm1@cornell.edu
Abstract
Known locally as Chem602, Information Literacy for the Physical Scientist is
a one-credit graduate course offered every spring at Cornell University. The
semester-long series of classes introduces physical scientists to the
extensive resources available in chemistry, the physical sciences and the
life sciences. Indexes, abstracts, handbooks, databases, librarians and
other fugitive resources in print and electronic formats are considered.
Each lecture is organized around like resources, specific searching skills
and common question types, with carefully prepared demonstrations and
exercises. Graduate and undergraduate students, faculty, staff and
librarians are encouraged to enroll or drop-in on individual sessions for
hands-on training. This poster will illustrate the approach of the
curriculum, provide sample lectures, exercises and evaluation criteria, and
outline the evolution of the course with the changing nature of information,
my growing experience and feedback from students.
CINF 64: Library and database assignments for
undergraduate chemistry majors
Ann D. Bolek, Science-Technology Library, The University of Akron,
Akron, OH 44325-3907, Fax: 330-972-7033, bolek@uakron.edu
Abstract
At The University of Akron, undergraduate chemistry majors are given library
and database assignments during their junior year in their Advanced
Chemistry Laboratory classes. During the first semester, they are assigned
searches in SciFinder Scholar, whereas during the second semester, they are
assigned searches in Beilstein and Gmelin CrossFire, the Web of Science, the
Cambridge Structural Database, various Web resources, and printed reference
books. This poster will list the sources used and provide examples of some
of the searches assigned.
CINF 65: Team Green: An integrated approach to teaching analytical
chemistry and chemical literacy
Mary Ellen Teasdale, James G. Gee Library - Science Reference, Texas
A&M University - Commerce, 2600 South Neal, Commerce, TX 75429, Fax:
903-886-5723, libmt@tamu-commerce.edu, and Anita I. Zvaigzne, Department of
Chemistry, Texas A&M University - Commerce
Abstract
How long would it take a person to die from inhalation of a poisonous gas?
When the gas cylinder spews into the open lab area, LD-50 and risk
assessment should already have been considered. Therefore, to develop
students’ appreciation for problems encountered by analytical chemists and
for using the chemical literature, Team Green was devised by a chemistry
instructor and science reference librarian. The Team Green problem assigned
to the students was to generate a mock Chemical Response Plan (CRP) for
first responders and community officials encountering chemical warfare
agents in a small rural community. This poster highlights how analytical
chemistry and chemical information can be integrated. The purpose of this
exercise is to teach undergraduate chemistry students chemical information
strategies in order to address the kinds of problems that might be
encountered in working in an industrial or community setting.
CINF 66: Using poster sessions in a chemical
information course
F. Bartow Culp, Mellon Library of Chemistry, Purdue University, West
Lafayette, IN 47907, bculp@purdue.edu
Abstract
In teaching a course in chemical information, the instructor is forever
reconciling the opposing forces of content inclusion with class time
availability. Even a full semester course is rarely more than a
one-credit/one-class-per-week offering - barely enough time to teach the
sources and skills necessary to fulfill minimal course objectives. Having
students prepare and present a poster session is one way to maximize the use
of limited class time. At Purdue University, a student poster project has
been a popular part of the chemical information course for several years. In
addition to the time savings mentioned above, there are other instructional
advantages to this program.
CINF 67: Balancing theory and practice in chemical information
instruction
Charles F. Huber, Davidson Library, University of California - Santa
Barbara, Santa Barbara, CA 93106, Fax: 805-893-8620, huber@library.ucsb.edu
Abstract
Most undergraduate and graduate students in chemistry don't intend to become
chemical information professionals. They only want the nuts and bolts of
searching the literature as easily and quickly as possible with the tools at
hand. But sometimes more theoretical concepts or historical background can
help make the students better searchers. Where to strike the balance?
Examples from my chemical literature course at UC-Santa Barbara will be used
to illustrate one approach.
CINF 68: Developing the better mousetrap: Creating chemistry course and
subject guides in a content management system
Teri M. Vogel, University Library, Georgia State University, 100
Decatur Street SE, MSC 8E0705, Atlanta, GA 30033-3202, Fax: 404-651-4315,
tmvogel@gsu.edu
Abstract
In 2003 Georgia State University Library began implementing a content
management system (CMS) for the fifteen liaison librarians to create Web
pages for their faculty and students. A CMS offers a number of advantages
for any library, most importantly the use of forms and templates to make
global changes and to create a uniform structure and look among pages
managed by multiple contributors. For the Chemistry Liaison, the CMS has
greatly streamlined the process of developing content-rich subject and class
guides to support library instruction. Standard instruction pages can be
created once, and then included in multiple guides with a mouse click. The
form/template style makes it easier to divide these guides into smaller
units, a standard rule of Web usability principles. The result is ability to
develop highly sophisticated resource guides for specialized topics like
SciFinder and Beilstein, while still creating pages that patrons can easily
navigate and use.
CINF 69: Experiments in teaching information
skills to chemical & engineering students
Erja Kajosalo, Libraries, Massachusetts Institute of Technology,
Building 14S-134, 77 Massachusetts Ave, Cambridge, MA 02139, kajosalo@mit.edu
Abstract
It is hard to get an attention of busy chemistry faculty and students, and
as a chemistry librarian I am constatly trying different approaches in
informing chemistry and chemical engineering faculty and students of the
existence and use of the libraries' vast chemical information resources.
There are individual research appointments, and hands-on sessions on major
chemistry databases. Library instruction session might be a part of the
course syllabus, or we create a course-specific web page. Our users can
attend our open labs and lectures about chemistry resources, and we teach
administrative staff how to find articles for faculty from their desktop.
The latest addition is a seminar series on chemical information intruducing
several databases to graduate students and postdocs in different
departments. This poster will highlight these different approaches and what
has worked for us.
CINF 70: Printed
Beilstein Handbook: An enduring resource in organic chemistry
Philip Barnett, Science/Engineering Library, City College of New York
(CUNY), Convent Avenue at 138th Street, New York, NY 10031, Fax:
212-650-7626, pbarnett@ccny.cuny.edu
Abstract
For over a century, the printed Beilstein Handbook of Organic Chemistry has
been a nonpareil source of data on properties of organic compounds. Until
about a decade ago, many organizations collected most or all of the printed
volumes. While many users now access Beilstein on either the subscription
based CrossFire® or the online Beilstein database, many other
users are bound to the printed handbook because they either cannot afford
CrossFire® or they lack a sufficient budget for extensive
searching of the database. Moreover, the venerable printed version has a
unique feature: one can browse to see how compounds related to a compound of
interest are prepared, even if the compound of interest has not yet been
synthesized. New users of the massive printed handbook are often intimidated
by the difficulty of learning the complex and multi-layered rules for
locating compounds in the printed volumes. However, tutorials and user aids
like the ones in the Clearinghouse for Chemical Information Instructional
Materials, and a small computer program, SANDRA®, from the
Beilstein Institute, enable new and occasional users to readily locate
substances in these books. One such tutorial (http://www.indiana.edu/~cheminfo/33-16.html)
explains both the layout of the handbook and how to use SANDRA®.
This tutorial, accompanied by an appropriate assignment (such as finding
some physical properties of a given compound in the main and all
supplementary volumes) will teach mastery of the handbook. At the same time
this regimen will reassure students that they can find any desired substance
in this printed work.
CINF 71: Publishing in the Chemical Information
Instructor feature of the Journal of Chemical Education
Andrea Twiss-Brooks, John Crerar Library, University of Chicago, 5730
S. Ellis Ave, Chicago, IL 60637-1403, atbrooks@uchicago.edu
Abstract
Current ACS Committee on Professional Training guidelines require teaching
of “the systematic use of chemical information.” 1 Skilled and inventive
instructors are developing new strategies and programs to fulfill this
guideline and produce chemists that know how to find, critically evaluate,
and use chemical information. The Chemical Information Instructor feature of
the Journal of Chemical Education provides instructors with a forum to share
practical information related to teaching chemical information literacy and
skills with colleagues who face the same challenges. Information is provided
in print, and on the Web via JCE Online. Topics of submissions include
integration of information instruction into one or more courses, integration
of WWW sources into instruction, instruction on specific types of
information (e.g., organic reactions) or specific types of materials (e.g.,
patents) or specific sources and databases (e.g., Chemical Abstracts), and
teaching techniques. A brief history of the feature, a bibliography of
previously published articles, and information on submission of articles
will be presented.
1) American Chemical Society. Committee on Professional Training.
Undergraduate Professional Education in Chemistry: Guidelines and Evaluation
Procedures. Spring 2003, p.9
CINF 72: Kinases, homology modeling, and high
throughput docking
David J. Diller, Molecular Modeling, Pharmacopeia, Box 5350,
Princeton, NJ 08543-5350, Fax: 609-655-4187, ddiller@pharmacop.com
Abstract
Over the past few years we have developed molecular docking software
intended for discovery combinatorial library design. The two main
considerations in the design were thus speed and utility with homology
models. Significant effort was put into validating the approach in the
context of homology models for kinase targeted library design. In this talk
we briefly discuss the philosophy behind the design and the validation
studies. Furthermore, we discuss how we have used the results of the study
in kinase targeted library design. Finally, we discuss the success of the
libraries designed with this procedure.
CINF 73: Virtual screening for kinase inhibitors
Paul D. Lyne, Cancer Discovery, AstraZeneca, 35 Gatehouse Drive,
Waltham, MA 02451, paul.lyne@astrazeneca.com
Abstract
A virtual screen of a subsection of our corporate collection was performed
for checkpoint-1 kinase using a knowledge-based strategy. This involved
initial filtering of the compound collection by application of generic
physical properties followed by removal of compounds with undesirable
functionality. Subsequently a 3-D pharmacophore screen for compounds with a
kinase binding motif was applied. The remaining compounds were docked and
rescored, resulting in 103 compounds being tested. This yielded 36 hits in
the IC50 range of 110nM to 68uM, corresponding to four chemical classes.
CINF 74: EA-Inventor: Using vHTS scoring functions for de novo
design
Robert S. Pearlman and Karl M. Smith, Optive Research, Inc, 12331-A
Riata Trace Parkway -- Suite 110, Austin, TX 78727, bob.pearlman@optive.com
Abstract
Virtual HTS involves application of a scoring function to a specified,
pre-determined set of structures. De novo design involves application
of a scoring function to a dynamically evolving set of structures. De
novo design also involves the application of a “structure modifying
engine” to generate new structures and control the process by which
structures with improved scores are evolved. Previous efforts to develop
de novo design packages have focused, primarily, on developing “the best
possible scoring function.” This is unfortunate for two reasons. First, the
choice of “best” scoring function varies greatly from one discovery project
to the next (and from one scientist to the next). Second, insufficient
attention has been devoted to developing “the best possible structure
modifying engine.”
We will describe an exceptionally complete and robust structure modifying
engine (EA-Inventor) which offers two extremely important features. First,
the nature of the structural modifications (and, hence, resulting
structures) can be “tuned” to best suit the needs of particular discovery
projects. Second, the engine can easily be used in conjunction with
literally any scoring function or composite scoring function –
whatever function is deemed most appropriate for the particular discovery
project.
CINF 75: High-throughput molecular docking for lead discovery
Diane Joseph-McCarthy and Juan C. Alvarez, Chemical and Screening
Sciences, Wyeth Research, 200 CambridgePark Drive, Cambridge, MA 02140, Fax:
617-665-5682, DJoseph@wyeth.com
Abstract
High-throughput virtual screening of large three-dimensional molecular
databases enables the identification of novel small molecule drug leads for
biologically relevant targets. Accurate molecular docking of small molecules
to a target structure requires adequate sampling and accurate scoring of
each library ligand in the target binding site. Our pharmacophore-based
docking approach allows for efficient sampling of the ligand conformations
and orientations in the target structure. The use of a fast scoring filter
followed by a more rigorous scoring function to rank selected hits will be
discussed. In particular, the utility of various scoring schemes for
identifying viable leads in test cases as well as in a therapeutic target
screen will be presented.
CINF 76: Automating and improving virtual screening of large compound
databases
Niu Huang1, John Irwin2, Chakrapani
Kalyanaraman2, Brian Shoichet2, and Matthew P Jacobson2.
(1) Department of Biopharmaceutical Sciences, University of California, San
Francisco, 600 16th St., Suite N474E, San Francisco, CA 94143, nhuang@salilab.org,
(2) Department of Pharmaceutical Chemistry, University of California, San
Francisco
Abstract
Despite well-known weaknesses, molecular docking is now one of the most
practical techniques to leverage structure for ligand discovery. We have
developed a docking and rescoring protocol to computationally screen
chemical databases containing millions of compounds with minimal user
intervention. Docking was performed using the DOCK 3.5.54 program with a
grid-based electrostatic and van der Waals interaction energy evaluation
including a partial ligand desovlation energy correction. This fully
automated docking approach was evaluated by the extent to which known
binders were enriched against a background of drug-like decoys and compared
favorably with enrichments obtained by an expert. The binding poses of top
scoring compounds from docking was submitted to further refinement and
rescoring using an all-atom force field (OPLS AA) and implicit solvent model
(Generalized Born); the use of a rapid multi-scale Truncated Newton energy
minimization algorithm enabled this refinement stage to be completed with
less than one minute per ligand. Significant improvement in enrichment was
observed for most of the systems studied.
CINF 77: Navigating high-throughput docking
results
Keana Scott, Noel Southall, Trung Nguyen, and Dr Ajay, Informatics,
Celera Genomics, 45 W. Gude Drive, Rockville, MD 20850, Fax: 240-453-3303,
keana.scott@celera.com
Abstract
High-throughput docking results are often subjected to strict filters that
are based on multiple scoring functions and applied in linear fashion to
reduce the docked poses to a manageable number for visual inspection.
Although filters reduce the number of false positives, they also decrease
statistical power in the docking exercise by increasing the number of false
negatives. Instead, we have developed a flexible tool that 1) allows the
user to navigate through the entire binding mode hypothesis space rather
than a small subset of individual poses, 2) does not preclude interesting
unanticipated binding modes, 3) incorporates multiple in-house developed
scoring functions, and 4) enables us to leverage a modeler’s intuition. This
flexibility is achieved through a Java-based user interface that allows for
mathematical/logical operations in hypothesis space and works hand-in-hand
with PyMol for visualization and an Oracle backend for data storage.
CINF 78: Beyond the limits in early ADME prediction to boost v-HTS
Jacques R. Chretien1, Han van de Waterbeemd2,
Nadege Piclin1, Christophe Wechman3, and Marco Pintore1.
(1) BioChemics Consulting, Innovation Center, 16 L. de Vinci, 45074 Orleans
cedex 2, France, Fax: + 33 2 38 41 72 21, jacques.chretien@univ-orleans.fr,
(2) PDM, Department of Drug Metabolism, Pfizer Global Research and
Development, (3) LBLGC / CBI, UPRES EA 1207, University of Orleans
Abstract
Appropriate pharmacokinetic properties are important for the success of a
drug discovery program. There is a need to incorporate ADME considerations
already in the first phases of the drug discovery, more particularly in
virtual design and virtual screening (v-HTS). Such procedures will be able
to predict ADME properties of any molecule beyond the limits of the Lipinski
rules. Recently, new computational methods based on Genetic Algorithms and
Fuzzy Logic have been developed by us allowing to develop a number of early
ADME predictors [1]. In this contribution, their application to the main
pharmacokinetic properties, i.e. oral absorption, bioavailability, volume of
distribution and clearance, will be discussed. All models generated were
validated by cross-validation, test set and Y-sampling procedures, and most
of them were able to predict correctly ADME properties with prediction rates
higher than 65-70%. Moreover, the proposed techniques showed robustness and
a prediction power higher than those derived from other comparable methods.
References: [1] Pintore M, van de Waterbeemd H, Piclin N, Chrétien J.,
Prediction of oral bioavailability by adaptive fuzzy partitioning, Eur J Med
Chem (2003), 38, 427-431.
CINF 79: Improving the workflow and accuracy of in silico ADME/Tox
prediction
Gregory M. Banik and Michelle D'Souza, Informatics Division, Sadtler
Software & Databases, Bio-Rad Laboratories, 3316 Spring Garden Street,
Philadelphia, PA 19104-2596, Fax: 215-662-0585
Abstract
In silico ADME/Tox prediction can shorten the research-to-market cycle and
eliminate wasted effort in pharmaceutical R&D through the identification and
evaluation of possible problems with a potential lead compounds. This
presentation will demonstrate how drug discovery professionals can generate
ADME/Tox profiles for potential lead compounds and accelerate lead
generation with: simultaneous side-by-side prediction of multiple
properties, consensus predictions using multiple models for more accurate
results, validation tools to verify models, seamless data mining, and an
integrated toolset for improved workflow. This session will also demonstrate
how the software can be used not only as an evaluation tool for assessing
fundamental ADME/Tox parameters, but also as an informatics system for
mining, managing, searching, and communicating the knowledge obtained from
such assessments.
CINF 80: Classpharmer and the quest for privileged substructures
Dora Schnur, Computer Assisted Drug Design, Bristol-Myers Squibb,
P.O. Box 5400, Princeton, NJ 08543, and Mark A. Hermsmeier, New Leads
Chemistry, Bristol-Myers Squibb
Abstract
With the onslaught of data that has arisen from solving the human genome,
creation of libraries and screening decks that are directed toward families
of receptors such as GPCR’s, kinases, nuclear hormones, etc. has replaced
generation of libraries and screening decks based primarily on diversity.
Although diversity-based design still plays a role, particularly for orphan
receptors and for receptors with no known small molecule ligands, more
knowledge based approaches are required for target class design. A standard
approach involves the use of privileged substructures. These “target class
active” fragments or substructures may be found by various methods. This
presentation focuses on the use of Classpharmer(TM) to find such
substructures for target class compound sets from the MDDR as derived from
Schuffenhauer,Jacoby, et al: “An Ontology for Pharmaceutical Ligands….”,
JCICS 2002, 42, 947-955. It also examines the validity of the concept of
"privileged substructure".
CINF 81: Chemometric approaches to virtual
screening
Alexander Tropsha, Scott Oloff, Shuxing Zhang, and Min Shen,
Laboratory for Molecular Modeling, School of Pharmacy, University of North
Carolina at Chapel Hill, CB # 7360, Beard Hall, School of Pharmacy, Chapel
Hill, NC 27599-7360, Fax: 919-966-0204, alex_tropsha@unc.edu
Abstract
We discuss novel chemometric approaches to both ligand and receptor based
virtual screening, which characterize both ligands and receptors (if
available) in multidimensional space of chemical descriptors. In ligand
based screening, we employ rigorously validated QSAR models to mine chemical
databases for compounds with high predicted activity. We demonstrate that
this approach yields an exceptionally high experimental hit rate in
identifying anticonvulsant compounds from a set of 250,000 molecules. We
also report on a novel approach to identifying Complementary Ligands Based
on Receptor Information (CoLiBRI). CoLIBRI transforms chemical structure of
both ligands and their complimentary active sites into the high-dimensional
descriptor space and uses specially developed chemical similarity metrics to
mine target’s complementary ligands from large databases. The results
illustrate that CoLiBRI is capable of identifying all known ligands of 260
test binding sites within the top 1% of the database of ca. 60,000 compounds
in 95% of all cases.
CINF 82: Functional group fingerprints:
Augmenting hit and lead identification
James R. Arnold, Charles L. Lerman, and James R. Damewood, CNS
Chemistry, AstraZeneca, 1800 Concord Pike, Wilmington, DE 19850, Fax:
302-886-5382, james.arnold@astrazeneca.com
Abstract
It has been estimated that roughly 70% of drug discovery projects must be
approached by ligand-based methods, as many targets are not currently
amenable to structural studies. We present a novel ligand-based method
called Functional Group Fingerprinting. This method classifies medicinally
relevant functional groups in molecules using approximately 400 defined
functional groups. It creates bitstrings that are used to calculate
similarity scores between known actives and either databases or libraries of
compounds. In this presentation we will show completeness and orthogonality
of the functional group assignments in medicinally relevant compounds.
Functional Group Fingerprinting also recovers different sets of actives than
those recovered with other fingerprint methods. We will show the enrichment
rates observed with this method in greater than 500 target classes within
the MDDR are comparable or superior to existing methods. The method recovers
on average greater than 60% of the active compounds in less than 1% of the
ranked MDDR target classes. This permits fewer compounds to be screened in
the hit or lead identification stages in order to identify a sufficient
number of chemical classes for lead generation to progress on a given
target. That results in reduced depletion of the corporate compound
collection, more targets being evaluated, and more efficient identification
of lead series for prioritization.
CINF 83: Steric multiplet fingerprints as screens in high-throughput
screening
Essam Metwally1, Robert Clark2, and Peter C.
Fox1. (1) Tripos Inc, 1699 South Hanley Road, Saint Louis, MO
63144, emetwall@tripos.com, (2) Discovery Software, Tripos Inc
Abstract
Rapid screening of large chemical databases for potential lead compounds has
become ever more important as the number of known biological targets has
risen dramatically. Using fully flexible 3d searching on a large database is
prohibitively time consuming to be routinely used as a screening method,
thus a rapid screen that allows the majority of compounds to be filtered out
before a 3d search is run is highly desirable. A number of methods have been
developed to rapidly screen databases utilizing fragment-based fingerprints,
and more recently pharmacophoric feature based fingerprints. The steric or
shape component of each molecule is disregarded in these types of
fingerprints. Screening on a fingerprint descriptor that encodes the shape
information of a query may be a valuable addition to the fragment or
pharmacophore-based screens.
We have extended Tripos' tuplet technology to include the ability to use
steric multiplet fingerprints, which encode flexible shape information of
the database molecules, either alone or in concert with pharmacophoric
feature multiplets. The definition, creation and storage methodologies for
these fingerprints will be discussed. Examples of the use of these
fingerprints as database screens will also be covered.
CINF 84: From gene to lead: In silico
warfare on the West Nile virus
Luke S. Fisher, Dana Haley-Vicente, and Anne Marie Quinn, Lead
Identification and Optimization, Accelrys Inc, 596 Midnight Pass, Antioch,
IL 60002, Fax: 240-248-3096, lfisher@chemist.com
Abstract
Can we produce reliable structural models of the proteins encoded by the
West Nile virus genome even when sequence identity is low among homologs?
Such structural information is critical to further efforts to design drugs
to fight the onslaught of disease. Here we show that the Discovery Studio®
(DS) GeneAtlas pipeline can be used to produce reliable structural and
functional annotation of the proteins encoded by the West Nile virus genome.
The 3D homology models generated have been used as the biological targets
for lead finding experiments that include a combination of docking and de
novo design. New chemotypes identified have also been prioritized based on
their 'drug-like' characteristics and synthetic feasibility.
CINF 85: Automation and deployment of virtual screening to the
discovery organization
Robert D Brown, Andrei Caracoti, and Rahim Lila, SciTegic, Inc, 9665
Chesapeak Dr. #401, San Diego, CA 92123, Fax: 858 279 8804, rbrown@scitegic.com
Abstract
For virtual screening to have a tangible impact on the Discovery process, an
informatics infrastructure must be developed to underpin the scientific
algorithms. This allows the virtual screening methodologies to be
transformed from manual processes restricted to a computational chemistry
lab into automated processes deployed them to the wider discovery
organization. Data pipelining provides a paradigm that allows for the
automation of the virtual screening process and allows web deployment of
virtual screens to the chemists and biologists that need to apply the
results. We will describe this approach and its advantages with reference to
the integration of GOLD molecular docking from the Cambridge
Crystallographic Data Centre and FlexX from Tripos Inc into an automated
data pipelining process and we will show the deployment of that process
through a Web based tool.
CINF 86: Ultra-high throughput vHTS with neural networks
Victor S. Lobanov, 3-Dimensional Pharmaceuticals, Inc, 665 Stockton
Dr., Suite 104, Exton, PA 19341, Fax: 610-458-8249, victor.lobanov@3dp.com
Abstract
3D pharmacophore- and docking-based virtual screening involves intensive
computations that impose severe limitations on the number of compounds that
can be screened within a reasonable period of time. In contrast, artificial
neural networks trained with 1D and 2D molecular descriptors offer several
orders of magnitude higher throughput and can be applied to screen truly
massive collections. In this presentation, pros and cons of neural network
based virtual screening techniques are discussed and examples of neural
networks trained to predict activity and ADME properties are presented.
CINF 87: SARtree. A new method for analyzing and visualizing the
results from virtual and experimental screening of large complex chemical
libraries
Donovan N. Chin, Anuj Patel, R. Aldrin Denny, and Juswinder Singh,
Computational Drug Design, BiogenIdec, 14 Cambridge Center, Cambridge, MA
02142, donovan.chin@biogenidec.com
Abstract
This talk will describe a newly developed method at BiogenIdec for analyzing
and visualizing the results from virtual screening of large complex chemical
libraries. The method involves two unique steps. First, an algorithm to
recursively partition and keep track of chemical libraries into core
substructures, attached common sub-cores and unique chemical fragments.
Second, an interactive graphical "tree" that permits the analyst to
visualize the connection and relationships between the common and unique
chemical groups from step one. Property information--e.g. virtual screening
scoring, biological assay data, or both--can be overlaid on the graphical
tree to allow rapid identification of chemical fragment hotspots for a given
dataset. We will highlight the utility of SARtree on several chemical
datasets including CDK2 kinase from virtual screening. Finally, we will
demonstrate that SARtree is a powerful new way of quickly identifying
chemical structure-variation and -property relationships hidden in chemical
datasets. SARtree is therefore emerging as a useful tool for analyzing and
understanding the output from virtual screening, and as a new way of
tracking and visualizing (virtual) chemical libraries.
CINF 88: Searching the impossible: Feature trees
in fragment space
Marcus Gastreich, Sally Ann Hindle, and Christian Lemmen, BioSolveIT
GmbH, An der Ziegelei 75, 53757 Sankt Augustin, Germany, Fax: +49 2241 2525
525, marcus.gastreich@biosolveit.de
Abstract
FTrees is known to be an effective program for similarity searching. Based
on the feature tree descriptor, the similarity of two molecules is defined
as the score for the best possible alignment of the respective compared
trees. Thanks to the tree nature, this optimal alignment can be computed
very efficiently.
The step beyond simple A to B similarity calculations is an on-the-fly
assembly of molecule B from a fragment space such that virtual molecule B is
most similar to A. Due to the combinatorial nature of the problem, the size
of this fragment search space is roughly 10^18 compounds - which is
impossible to search sequentially.
We report on the generation of fragment spaces, technology to efficiently
search them, and example applications. Thanks to the availability of the
underlying Feature Trees as a Python module, the entire process can be
scripted and executed in parallel within an integrated Python environment.
CINF 89: Fast and accurate coarse-grained estimate of small molecule
binding free energies
Jun Shimada, Alexey V. Ishchenko, Kam Jim, David J. Lawson, Peter R.
Lindblom, Guosheng Wu, and JP Wery, Computational Drug Discovery,
Concurrent Pharmaceuticals, Inc, 502 West Office Center Drive, Fort
Washington, PA 19034, Fax: 215-461-2006, jshimada@concurrentpharma.com,
jwery@concurrentpharma.com
Abstract
A novel approach for the prediction of binding free energies will be
presented. This approach is characterized by three critical features: (1) a
coarse-grained physical model of the binding process, (2) trainability, and
(3) a sophisticated machine learning algorithm that maximally utilizes the
information from bioassays. When used against multiple pharmacologically
relevant targets, this scoring function has proven to be accurate and
generalizable outside of the training set. In virtual screening against
aspartyl proteases, nuclear receptors and kinases, this approach was able to
select inhibitors which, after synthesis, were shown to be active.
CINF 90: Building predictive models from high-throughput screening data
Paul E. Blower, Kevin P. Cross, Glenn J. Myatt, and Chihae Yang,
Leadscope, Inc, Columbus, OH 43215, pblower@leadscope.com
Abstract
Predictive models derived from high-throughput screening (HTS) data can be
useful for prioritizing compounds for further testing. However, HTS data is
typically of poor quality with many values out of range and wide variability
among replicate test results. Structure-based clustering often reveals an
irregular landscape, both in terms of the compound classes represented and
the distribution of active compounds across structural classes. Large
regions of the chemical space are devoid of activity. Indeed most compounds
are not active and not similar to active compounds and thus are of marginal
value for modeling activity. Even among active classes, the within class
active / inactive ratio may still be very unbalanced, or the range of
response values too narrow, or classes are too small to derive accurate
models. This presentation will survey problems of building predictive models
from large, heterogeneous screening sets and describe methods for addressing
them.
CINF 91: Virtual high-throughput screening: How
to boost the pharmacophore approach
Frédérique Barbosa, Molecular Modelling, Cerep, 128, rue Danton,
92500 Rueil Malmaison, France, Fax: 33 1 55 94 84 10, F.Barbosa@cerep.fr
Abstract
The virtual screening of large libraries is structure-based or ligand-based.
Structure-based virtual screening (docking) is time consuming and requires a
precise knowledge of the 3D structure of the target and of the various
binding contributions. For ligand-based screening, the only determining step
is the appropriate choice of descriptors and similarity metrics. A careful
pharmacophoric description of the 3D conformers of the ligands is required
to take into account the features responsible for binding. We use such an
approach to retrieve new lead compounds from large and chemically diverse
virtual libraries. We have built internally a virtual library of 108
chemically feasible compounds from >7000 building blocks (>1500 proprietary)
using validated chemistries. We use a so-called “ghost database” mechanism
that allows for the fast calculation of multiple conformers and
pharmacophoric fingerprints for each individual structure in the database.
Therefore extensive virtual screening with pharmacophores can be done within
tractable CPU time. The retrieved compounds are further analyzed by
predicting ADME-T properties with Cerep proprietary QSAR models based on
BioPrint® (>2000 drug and drug-like compounds tested across >170 in vitro
assays). This two stage approach accelerates the identification of promising
chemical structures for early drug discovery.
CINF 92: Reducing CYP-2 liabilities using pharmacophore hypotheses
derived from protein structures and inhibitors
Akbar Nayeem and Litai Zhang, Computer-Assisted Drug Design,
Bristol-Myers Squibb, Pharmaceutical Research Institute, P.O. Box 5400,
Princeton, NJ 08543-5400, Fax: 609-818-3545, akbar.nayeem@bms.com,
litai.zhang@bms.com
Abstract
The CYP-2 family of cytochrome P450s ranks among the most important drug
metabolizing CYP isoforms present in human liver, and numerous inhibitory
drug interactions of high clinical significance involving CYP 2D6 and 2C9
substrates have been described. With the goal of reducing the liability of
drug-drug interactions caused by possible inhibition of CYP 2C9, 2C19 and
2D6, 3D-pharmacophore models for each of these isoforms have been developed
using their respective homology models, known substrates, and our in-house
inhibitors from BMS. The pharmacophore hypotheses derived from these models
are presented and are shown to be useful in understanding the active site of
these isozymes. The in-silico models derived thusly are used to triage and
prioritize chemical library synthesis and reduce the potential liability of
drug-drug interactions caused by CYP-2 family inhibitions.
CINF 93: Interplay of docking, pharmacophores, and shape in virtual
high-throughput screening
Erik Evensen, Hans E. Purkey, Kenneth E. Lind, and Erin K. Bradley,
Computational Sciences, Sunesis Pharmaceuticals Inc, 341 Oyster Point Blvd.,
South San Francisco, CA 94080, Fax: 650-266-3501, ee@sunesis.com
Abstract
We have observed recently that post-filtering docking results using
pharmacophore models leads to improved enrichments in virtual screening
exercises over docking or pharmacophore screening alone. This
counter-intuitive insight leads to further questions that point to potential
areas for improvement in virtual high-throughput screening. For example, it
has been proposed that the improvement over pure pharmacophore-based methods
is because docking selects compounds that are shape complementary to the
target. We will present inquiries into improving pharmacophore
post-filtering and using shape filtering as a higher throughput surrogate
for docking. We evaluate the interplay and impact of these methods by
applying them to data sets obtained on multiple proteins from different
families.
CINF 94: Compound optimization tools: Designed by the scientists for
the scientists
Uwe Geissler, LION bioscience AG, Waldhofer Str. 98, Heidelberg
D-69123, Germany, uwe.geissler@lionbioscience.com, and Manish Sud, LION
bioscience Inc
Abstract
During compound optimization stage of a discovery cycle, the bench
scientists are mainly interested in not only figuring out the key structural
features responsible for activity, selectivity, and favorable ADME
properties but also what structural changes need be made to improve these
characteristics. In order to address these questions, a variety of search
and analysis methodologies, along with visualization tools for structural
and numerical data, are routinely deployed at the desktops. Unless these
tools are easy-to-use and address relevant questions, the bench scientists
are seldom interested in using them. In collaboration with an external
customer, we have developed a compound optimization tools environment which
provides easy-to-use search, analysis and visualization capabilities.
Additionally, compute services framework is also available for deploying any
internal or third party applications. Interactive visualization and analysis
capabilities include: chemistry centric spreadsheet, 2D/3D scatter plots,
profile and multi series plots, and 2D/3D histograms, similarity searching,
clustering, R-group deconvolution, molecular descriptors calculation, and
others. We present an example of using these tools to address various
questions which come up during compound optimization.
CINF 95: HierS - hierarchical scaffold clustering
Steven J. Wilkens, Jeff J. Janes, and Andrew I. Su, Computational
Discovery, Genomics Institute of the Novartis Research Foundation, 10675
John Jay Hopkins Drive, C115, San Diego, CA 92121, swilkens@gnf.org
Abstract
An exhaustive ring-based algorithm has been developed to provide an
intuitive approach to compound clustering. The recursive algorithm rapidly
identifies all ring-delimited substructures within a compound. Molecules are
grouped by shared ring substructures (scaffolds) so that common scaffolds
obtain higher membership and greater importance. Once all of the scaffolds
are identified, hierarchical structural relationships are established. The
complex network of hierarchical relationships is then utilized to navigate
compounds in a structurally directed fashion. The utility of this approach
is demonstrated by providing readily interpretable model for chemical
diversity in different compound sets. In addition, a web-based application
has been developed which incorporates this algorithm in order to allow for
the interactive analysis of the diverse sets of compounds that are produced
from high-throughput screening. Biological data is coupled to scaffolds by
the inclusion of activity histograms, which indicate how the compounds in
each scaffold class performed in other screens.
CINF 96: Data handling in the NIST Chemistry WebBook
Peter J. Linstrom, Physical and Chemical Properties Division, NIST,
Building 221, Room A111, 100 Bureau Drive, Stop 8380, Gaithersburg, MD
20899-0830, Fax: 301-896-4020
Abstract
The NIST Chemistry WebBook (http://webbook.nist.gov/) is a web site which
provides a wide range of chemical and physical property data. The site, in
operation since 1996, has evolved to met the demands of new data types and a
diverse and growing user base. The data handling systems used by the site
have to address some common chemical informatics challenges: proper
identification of chemical species, specification of property values and
meta-data, and graphical representation of chemical structures and
spectroscopic data. This talk will describe how the internal architecture of
the site has evolved to meet these challenges. Topics to be discussed
include data structures, unit conversions, and structure processing.
Applications involving the new IUPAC-NIST chemical identifier will be
discussed.
CINF 97: TraX: An integrated system for drug discovery workflow
scheduling and tracking
Daniel A Gschwend1, Rebecca J. Carazza1, and
Sergio H. Rotstein2. (1) Research Informatics, ArQule Inc, 19
Presidential Way, Woburn, MA 01801, gschwend@arqule.com, (2) ArQule, Inc
Abstract
An efficient drug discovery process requires multiple disciplines to
coordinate their efforts in a systematic and coherent manner. Often this
goal is obstructed by the lack of inter-departmental communication and
inter-departmental awareness of resource allocation. Even in a small company
environment, much effort can be wasted through poorly coordinated actions
and unexpected events. This presentation will describe TraX, an integrated
resource planning and workflow tracking environment developed to support
ArQule's drug discovery efforts. This system enables all of our researchers
to be aware of all work going on within our drug discovery efforts and to
anticipate the workload coming their way.
CINF 98: MapMaker: An integrated compound library
design tool
Daming Li and Sergio H. Rotstein, ArQule, Inc, 19 Presidential Way,
Woburn, MA 01801, dli@arqule.com
Abstract
The design of a compound library requires a number of disparate steps,
including reagent selection, product enumeration, the computation of
properties of the enumerated products and the analysis of these properties
in the context of the library as a whole. This process often involves a
number of different software products across multiple operating systems, as
well as the import, export and transfer of compound and property data
between these systems. The complexity of the process often limits library
design activities to domain experts. MapMaker is a library design tool that
integrates the steps through a web-based user interface. In effect, MapMaker
eliminates most of the technical complexity of the library design process,
enabling synthetic chemists to carry out their own library design without
requiring expert assistance
