#238 - Co-sponsored Sessions

ACS National Meeting
Fall, 2009
Washington, DC


COMP - Computational Chemistry in the Discovery & Development of Novel Anti-Infective Agents
Walter E. Washington Convention Center 143 A
Organized by: G. Scott Weston, Ryszard J. Czerminski, John I. Manchester
8:20   Introductory Remarks
8:30 23 2'-F-2'-C-Methyl nucleosides for the treatment of HCV: From discovery to the clinic
Michael J. Sofia, Pharmasset Inc, 303-A College Road East, Princeton, NJ 08540

Hepatitis C is a global health problem with over 170 million individuals infected with the hepatitis C virus (HCV). Infection with HCV has been shown to lead to chronic liver disease, cirrhosis and eventually hepatocellular carcinoma. Currently, the standard of care is a combination of interferon-alpha and ribavirin, however, this regimen has limited effectiveness and is associated with debilitating side-effects. The search for direct acting antiviral agents has lead to the discovery of R7128 a nucleoside prodrug that inhibits the HCV NS5B polymerase. R7128 has demonstrated exceptional potency and safety in the clinic against genotype 1, 2 and 3 patients. In addition, PSI-7851, a nucleotide prodrug, showed increased liver exposure of the active triphosphate metabolite in laboratory animals and has also entered clinical evaluation. The discovery and current state of development for these two agents will be presented.

9:00 24 Modeling binding modes of HIV integrase inhibitors
Xiaowu Chen1, S. Swaminathan2, and James M. Chen, James.Chen@gilead.com2. (1) Dept. of Structural Chemistry, Gilead Sciences, Inc, 333 Lakeside Drive, Foster City, CA 94404, (2) Department of Structural Chemistry, Gilead Sciences, Inc, Foster City, CA 94404

Although significant progress has been made in HIV integrase inhibitor drug discovery, as demonstrated by FDA approval of Merck's raltegravir, there is still very limited understanding of inhibitor binding modes due to the lack of relevant crystal structures. In order to gain insight into the mechanism of inhibition and aid drug discovery effort, we have constructed an active site model of HIV-1 integrase complexed to both viral DNA and inhibitor. Our model suggests a common binding mode for potent integrase inhibitors that involves interactions with an induced active site hydrophobic pocket, formed upon viral DNA binidng. In addition, based on analysis of large number of nucleotidyltransferase, substrate, and Mg complex structures, we hypothesized that potent integrase inhibitors interact with only one of two bound active site Mg cations. To further validate the model, we made specific compounds and mutated key residues predicted to play an important role in inhibitor binding. These predictions were subsequently confirmed experimentally.

9:30 25 Identifying novel anthrax toxin lethal factor inhibitors via topomeric searching and docking/scoring
Elizabeth A. Amin, eamin@umn.edu1, Ting-Lan Chiu, tlchiu@umn.edu1, Derek Hook, hookx017@umn.edu2, Michael A. Walters, walte294@umn.edu2, and Satish Patil, pati0037@umn.edu1. (1) Department of Medicinal Chemistry, University of Minnesota, 717 Delaware St SE, Minneapolis, MN 55414, (2) Institute for Therapeutics Discovery and Development, University of Minnesota, 717 Delaware St SE, Minneapolis, MN 55414-2959

Anthrax is an acute infectious disease caused by the spore-forming, Gram-positive, rod-shaped bacterium Bacillus anthracis. The lethal factor (LF) enzyme is a zinc metalloenzyme secreted by B. anthracis as part of a tripartite exotoxin and is chiefly responsible for anthrax-related cytotoxicity. As LF can remain in the system for long after antibiotics have eradicated B. anthracis from the body, the preferred therapeutic modality is the administration of antibiotics together with an effective LF inhibitor. Such inhibitors must not only bind strongly to the receptor but must also possess excellent ADMET profiles. Although LF has attracted much attention as a drug target, few published inhibitors have demonstrated activity in cell-based assays and no LF inhibitor is currently available as a therapeutic or preventive agent. Here we present a novel virtual screening protocol which, together with experimental high-throughput screening, was able to identify nine new non-hydroxamic acid small molecules functioning as LF inhibitors with low micromolar-level inhibition against that target. A key topomeric searching component of this protocol was able to prioritize twenty-two thousand compounds from an initial dataset of approximately thirty-five million non-redundant structures. Compounds identified by this method were subsequently subjected to docking and scoring and drug-like (ADME-related) filtering protocols. Among the nine new hits, none of which was previously identified as a LF inhibitors, seven demonstrated experimental activity against LF less than 50 micromolar. Three of the top hits that exhibited single-digit IC50 values may potentially serve as scaffolds for lead optimization. Each of these three hits demonstrates a different zinc-binding mechanism predicted by docking and scoring; future work is planned to experimentally assess predicted binding modes by means of X-ray crystallography.

10:00   Intermission
10:15 26 Fragment-based molecular docking in inhibitor discovery against CTX-M class A β-lactamase
Yu Chen, chen@blur.compbio.ucsf.edu, Department of Pharmaceutical Chemistry, UCSF, 1700 4th ST, RM#501, QB3 Building, San Francisco, CA 94158-2330 and Brian Shoichet, shoichet@cgl.ucsf.edu, Department of Pharmaceutical Chemistry, University of California, San Francisco, 1700 4th Street, QB3 Building, Room 508D, San Francisco, CA 94143

Fragment screens have successfully identified new scaffolds in drug discovery, often with relatively high hit rates (5%) using small screening libraries (1,000-10,000 compounds). This raises two questions: would other interesting chemotypes be found were one to screen all commercially available fragments (>300,000), and does the success rate imply low specificity of fragments? We used molecular docking to screen large libraries of fragments against CTX-M beta-lactamase, one of the most common extended-spectrum beta-lactamases in many regions of the world and also a challenging target for inhibitor discovery. Ten mM-range inhibitors were identified from the 69 compounds tested. The docking poses corresponded closely to the crystallographic structures subsequently determined. Intriguingly, these initial low affinity hits showed little specificity between CTX-M and an unrelated beta-lactamase, AmpC, which is unusual among beta-lactamase inhibitors. This is consistent with the idea that the high hit rates among fragments correlate to a low initial specificity. As the inhibitors were progressed, both specificity and affinity rose together, leading to the first micromolar-range non-covalent inhibitors against a class A beta-lactamase.

10:45 27 Design and optimization of novel peptide deformylase inhibitors as new antibacterial agents
Kelly M. Aubart, Kelly.M.Aubart@gsk.com1, Andrew B. Benowitz1, Xiangmin Liao1, Joseph M. Karpinski1, Jinhwa Lee2, Jason Dreabit1, Yuhong Fang1, Andrew Knox1, Stephanie Kelly1, Nino Campobasso3, Chaya Duraiswami3, Kate J. Smith3, Maxwell Cummings4, Jacques Briand3, Swarupa Kulkarni5, Thomas F. Lewandowski6, Peter DeMarsh6, Rimma Zonis6, Lynn McCloskey6, Stephen Rittenhouse6, Siegfried B. Christensen7, Magdalena Zalacain6, and Martha Head3. (1) Medicinal Chemistry, Infectious Diseases CEDD, GlaxoSmithKline, 1250 South Collegeville Road, Collegeville, PA 19426, (2) Green Cross Corp, 303 Bojeong-dong, Giheung-gu, Yongin, 446-770, South Korea, (3) Molecular Discovery Research, GlaxoSmithKline, 1250 South Collegeville Road, Collegeville, PA 19426, (4) 3-Dimensional Pharmaceuticals, 665 Stockton Drive, Exton, PA 19341, (5) Oncology Business Unit, Novartis, Florham Park, NJ 07932, (6) Microbiology, Infectious Diseases CEDD, GlaxoSmithKline, 1250 S.Collegeville Road, Collegeville, PA 19426, (7) Virtual Proof of Concept Discovery Performance Unit, GlaxoSmithKline, 709 Swedeland Road, King of Prussia, PA 19406

Polypeptide Deformylase (PDF) is a metalloenzyme that has garnered much attention within the pharmaceutical industry as a promising target for the development of novel antibacterial agents. This enzyme catalyzes the removal of a formyl group from the N-terminal methionine of newly synthesized bacterial proteins, a deformylation process that is essential for bacterial survival. PDF is a relatively small protein (20-25 kD) that has proven to be amenable to X-ray crystallography studies. We have capitalized on this readily available structural information to design multiple series of novel non-peptidic inhibitors. The design and successful optimization of these PDF inhibitors will be discussed.

11:15 28 De novo design of novel polypeptide deformylase (PDF) inhibitor templates with broad spectrum antibacterial activity
Chaya Duraiswami, Chaya.2.Duraiswami@gsk.com1, Robert A Daines2, Nino Campobasso3, Mythili Vimal4, Israil Pendrak2, Magdalena Zalacain5, and Kelly M. Aubart, Kelly.M.Aubart@gsk.com6. (1) Computational and Structural Sciences, GlaxoSmithKline Pharmaceuticals, 1250 South Collegeville Road, UP-1110, Collegeville, PA 19426, (2) Dept. of Chemistry, GlaxoSmithKline, 1250 South Collegeville Road, UP-1110, Collegeville, PA 19426, (3) Molecular Discovery Research, GlaxoSmithKline, 1250 South Collegeville Road, Collegeville, PA 19426, (4) Department of Discovery Medicinal Chemistry, GlaxoSmithKline, Harlow, United Kingdom, (5) Microbiology, Infectious Diseases CEDD, GlaxoSmithKline, 1250 S.Collegeville Road, Collegeville, PA 19426, (6) Medicinal Chemistry, Infectious Diseases CEDD, GlaxoSmithKline, 1250 South Collegeville Road, Collegeville, PA 19426

A broad-spectrum antimicrobial target must be conserved across all pathogens of interest within a therapeutic product profile, essential for bacterial growth, and either absent, substantially different or non-essential in humans. PDF meets all of these criteria and is one of the most promising unexploited bacterial targets in the search for new antibiotics with a novel mode of action. PDF (EC is a metalloprotease that removes the N-formyl group of the polypeptides as they emerge from the ribosome during or immediately after completion of the elongation process.

Structure-based design studies in conjunction with de novo design studies using Allegrow was employed to find novel backup templates with broad-spectrum activity for the PDF program. The results from these studies will be presented.

11:45 29 Discovery of novel small-molecule inhibitors of P. falciparum using the hybrid structure based method
Sandhya Kortagere, sandhya.kortagere@drexelmed.edu1, JM Morrisey1, J Bosch2, KD Laroiya1, T Daly1, WJ Welsh3, E Fan2, W Hol2, P Sinnis4, I Ejigiri4, LW Bergman1, and AB Vaidya1. (1) Department of Microbiology and Immunology, Drexel University College of Medicine, 2900 Queen Lane, Philadelphia, PA 19129, (2) University of Washington, Department of Biochemistry and Biological Structure, Seattle, WA, (3) Department of Pharmacology, University of Medicine and Dentistry of New Jersey-Robert Wood Johnson Medical School, Piscataway, NJ, (4) Department of Parasitology, New York University School of Medicine, New York, NY

A key component of host cell invasion by Apicomplexan parasites is the interaction between the carboxy terminal tail of myosin A and the myosin tail interacting protein-MTIP. Based on the co-crystal structure of P. knowlesi MTIP and a MyoA tail peptide and using Hybrid Structure Based virtual screening approach, a series of small molecules were identified as having potential to inhibit MyoA-MTIP interactions. Of the initial 15 compounds tested, a pyrazole urea compound inhibited P. falciparum growth with an EC50 of ~250 nM. Screening of an additional 51 compounds belonging to the same chemical class identified eight compounds with EC50 of ~300 nM and one with an IC50 of ~50 nM. Interestingly, the compounds appear to act at several stages of the parasite life cycle to block growth and development. Thermal melting studies of MTIP in the presence and absence of the compounds show that many of the compounds bind and stabilize MTIP. The pyrazole urea compounds identified in this study could be effective antimalarials since they competitively inhibit a key protein-protein interaction between MTIP and MyoA responsible for the gliding motility and invasive features of the malarial parasite.

12:15   Lunch Break
12:15   Introductory Remarks
1:40 53 Some observations on the quality of 3D QSAR data sets
Ryszard J. Czerminski, ryszard.czerminski@astrazeneca.com, AstraZeneca Pharmaceuticals LP, 35 Gatehouse Drive, Waltham, MA 02451, C Eyermann, Joe.Eyermann@astrazeneca.com, Infection Discovery, Cancer and Infection Research Area, AstraZeneca, R&D Boston Inc, 35 Gatehouse Drive, Waltham, MA 02451, and John I. Manchester, John.Manchester@astrazeneca.com, Infection Discovery, AstraZeneca Pharmaceuticals LP, 35 Gatehouse Drive, Waltham, MA 02451

Oxazolidinones are a novel class of antibiotics. However, off-target activity has limited the number of agents in this class that have appeared on the market. One such activity is inhibition of monoamine oxidase A (MAO-A). We present a 3D QSAR study MAO-A inhibition by a new set of about a hundred oxazolidinones using the recently introduced Simple Atom-Type Mapping Following Alignment (SAMFA) method. In SAMFA, traditional molecular field-based descriptors are replaced with force-field-like atom types at the atomic centers giving rise to those fields. Although this approach reduces the number of descriptors to the number of atoms for each molecule in a given data set, we show that for nine data sets, including the steroid benchmark, there is no difference between SAMFA and Comparative Molecular Field Analysis (CoMFA). In fact, in many cases SAMFA descriptors can be further simplified to represent only whether certain atomic positions are occupied among aligned sets of molecules, without significantly affecting q2. We propose that this observation stems from artifacts that arise from incomplete sampling of the biologically relevant chemical space within those data sets. Two diagnostic approaches for characterizing this sort of undersampling will be presented and used to demonstrate that the oxazolidinone data set is less susceptible to artifact.

2:10 54 AutoGrow: A novel algorithm for protein inhibitor design
Jacob D. Durrant, jdurrant@ucsd.edu, Biomedical Sciences Program, UCSD, 9500 Gilman Drive #0685, La Jolla, CA 92093-0685, Rommie E Amaro, ramaro@mccammon.ucsd.edu, Department of Chemistry & Biochemistry, University of California San Diego, 9500 Gilman Drive, 4206 Urey Hall - MC 0365, La Jolla, CA 92093-0365, and J Andrew McCammon, jmccammon@ucsd.edu, Howard Hughes Medical Institute, Department of Chemistry and Biochemistry and Department of Pharmacology, Center for Theoretical Biological Physics, University of California at San Diego, 9500 Gilman Drive, Mail Code 0365, La Jolla, CA 92093-0365

Trypanosoma brucei (T. brucei) is an infectious agent for which drug development has been largely neglected. T. brucei is endemic to Africa, where it can infect the central nervous system in humans and cause African sleeping sickness. One potential T. brucei drug target is RNA editing ligase 1 (TbREL1), a critical component of a unique mitochondrial mRNA-editing complex known as the editosome. TbREL1 is an excellent drug target because it is essential for T. brucei survival and has no close human homologues.

AutoGrow, a new program that combines the strengths of fragment-based growing, docking, and evolutionary algorithms, is used to add interacting moieties to NSC16209, a known TbREL1 inhibitor. Careful analysis of the top AutoGrow-generated ligands suggests that they bind TbREL1 in ways similar to ATP, the natural TbREL1 substrate. The compounds presented here may serve as valuable starting points for future drug-design efforts in the fight against Human African Trypanomiasis.

2:40 55 Computational models of the action of protegrin antimicrobial peptides: Transient ion diffusion and osmotic swelling
Dan Bolintineanu, boli0073@umn.edu1, Ehsan Hazrati, Allison A. Langham, langham@dtc.umn.edu1, Robert I. Lehrer2, H. Ted Davis1, and Yiannis N. Kaznessis, yiannis@cems.umn.edu1. (1) Department of Chemical Engineering and Materials Science, University of Minnesota, Minneapolis, MN 55455, (2) Department of Medicine, UCLA, Los Angeles

Protegrins are a class of highly effective antimicrobial peptides, believed to act primarily by permeabilizing the bacterial cell membrane. We have conducted molecular dynamics simulations of the membrane-embedded pore structure formed by protegrin. We have then used structures extracted from these simulations as input to a continuum electrodiffusion model, in order to quantify the electrical conductance characteristics of such pores, and obtained good agreement with previously published experimental data. Finally, we have modeled the effects of multiple pores on an entire cell, using data obtained from the molecular and continuum electrodiffusion models. We have been able to estimate the number of pores required to reproduce the experimentally measured potassium release rate from an E. Coli cell, as well as quantify the effects of ion exchange processes on osmotic swelling of cells. Combined with experimental data, these models provide a comprehensive picture of the permeabilizing mechanism of protegrin antimicrobial peptides.

3:10   Intermission
3:25 56 Design of new antibacterial drugs: Computational approaches that take advantage of the rapid generation of multiple co-crystal structures
John Finn, jfinn@triusrx.com, Trius Therapeutics, Inc, 6310 Nancy Ridge Dr, Suite 101, San Diego, CA 92121

New classes of antibacterial drugs with novel mechanisms of action are needed to combat bacterial resistance. To meet this challenge, we focus on novel (or underexploited) antibacterial targets and utilize structure-based drug design techniques. We have built a structural biology platform that generates multiple (2-6) structures per week per program. This structural data provides information needed to design compounds with spectrum, selectivity, antibacterial activity and drug properties. This talk will provide a critical overview of the role of computational chemistry in structure-centric antibacterial discovery programs. We will describe our computational chemistry experiences, including:


  • Lead Discovery: virtual screening and de novo design


  • Lead Optimization: LUDI evolution of leads, ligand docking and scoring, design of compounds with spectrum and selectivity, dealing with enzyme flexibility and design of drug-like properties


3:55 57 Heme oxygenase as antimicrobial target: Results from computer-aided drug design and experiment
Pedro E. M. Lopes, lopes@outerbanks.umaryland.edu, Angela Wilks, awilks@rx.umaryland.edu, and Alexander D. MacKerell Jr., amackere@rx.umaryland.edu. Department of Pharmaceutical Sciences, University of Maryland, 20 Penn St., Baltimore, MD 21201

A variety of life-threatening diseases including meningitis, pneumonia, cholera and dysentery are caused by Gram-negative pathogens. They have developed sophisticated mechanisms for iron acquisition, which is important for their proliferation and infectivity. In addition to iron acquisition many of these pathogens can also utilize heme as an iron source. The final step of iron acquisition from heme is oxidative cleavage by a heme oxygenase (HO). We hypothesize that HO may provide a potential target for drug development. In this work, we apply computer-aided drug design (CADD) virtual screening techniques to identify small molecules inhibiting Neisseria meningitidis HO. Several of the compounds were found to have KD values in the micromolar range for Neisseria meningitidis HO and Pseudomonas aeruginosa HO. Moreover, data from simple host-pathogen models indicates that such compounds have antimicrobial activity.

4:25 58 Methodologies for efficient knowledge-based antibody homology modeling
Johannes Maier, jmaier@chemcomp.com, Chemical Computing Group, Inc, 1010 Sherbrooke Street West, Suite 910, Montreal, QC H3A 2R7, Canada

Antibodies are globular proteins composed of two heterodimers with each set containing a heavy chain (VH) and light chain (VL). The binding to an antigen is in most antibodies facilitated by six loops, three originating from the VL domain, termed L1, L2 and L3, and three from the VH domain, termed H1, H2 and H3. Due to their modular composition and high target specificity antibodies have become increasingly attractive for use as drugs. Antibody Homology Modeling techniques have often been applied in generating therapeutically more effective antibodies. Here, we demonstrate a collection of procedures as well as an interface to meet the demands of effective antibody homology modeling. The application has flexible components allowing the integration of various work-flows associated with this specific form of modeling. The routines account for the particular structural composition of antibodies when searching for template candidates and building models. A knowledge-based approach is applied with an underlying database of antibody structures originating from the Protein Data Bank (PDB), clustered by class, species, subclass and framework sequence identity. A specially designed loop grafting routine allows for generation of xenogeneic antibody models.

Take-Home Message:


  • Fast and efficient generation of antibody models


  • Integration of various work-flows associated with antibody homology modeling


  • Accounting for the structural composition of antibodies when searching for candidates and model building


  • CDR Loop grafting


4:55 59 Prediction of drug resistance using all-atom molecular simulations
Robert C. Rizzo, rizzorc@gmail.com, Department of Applied Mathematics and Statistics, Stony Brook University, Stony Brook, NY 11794-3600

Robust prediction of protein-ligand binding and drug resistance remains a difficult and challenging problem despite great strides made in both rigorous and more approximate free energy calculation methods. In this talk, we present our experiences using all-atom molecular dynamics followed by post-processing methods for estimation of binding free energies with application to the drug targets neuraminidase and epidermal growth factor receptor. Results of our optimization efforts, to improve virtual screening procedures using the program DOCK, will also be presented which focus on development of efficient protocols for reproduction of crystallographically observed binding poses using rigid, fixed anchor, and flexible ligand docking for a wide variety of targets.


COMP - Structure Activity Relationship Knowledgebases
Walter E. Washington Convention Center 147 A
Organized by: Evan Bolton, Stefan Senger
9:00   Introductory Remarks
9:05 8 Detection, assignment, and analysis of multiple scaffolds for medicinal chemistry project databases
Alex M. Clark, aclark@chemcomp.com, Research & Development, Chemical Computing Group, Inc, 1010 Sherbrooke St West, Suite 910, Montreal, QC H3A2R7, Canada

Analysis of structure-activity data for lead optimization often involves simultaneously classifying several series of analogous compounds according to scaffolds and R-group substituents. We have developed new algorithms for detection and analysis of multiple common scaffolds, and an interactive web-based report for examining the relationship between structure and activity.

The method for scaffold analysis advances the state of the art in the following ways:


  • The scaffold detection method finds multiple related common scaffolds, which will be aligned to each other in order to estimate common orientation


  • The assignment of scaffolds to molecules takes into account degeneracy, such as is the case for symmetrical scaffolds, in order to minimize the resulting R-group diversity


  • If partial information about the scaffolds is already available, this can be used to influence or override the automated methods

The results of this analysis are used to create a report, in which:


  • Molecules are rendered in 2D showing aligned scaffolds and implied R-groups


  • Tools for structure-activity analysis include correlation tables, activity estimation, fragment analysis, property graphs and navigation of similarity space


  • The report uses standard cross-platform HTML/JavaScript features which can be rendered by all modern browsers


9:35 9 Online chemical modeling environment: models
Iurii Sushko, Sergii Novotarskyi, Anil Kumar Pandey, Robert Körner, and Igor V. Tetko, itetko@vcclab.org. Helmholtz Zentrum Muenchen German Research Center for Environmental Health, Institute of Bioinformatics and Systems Biology, Ingolstaedter Landstrasse 1, Neuherberg, D-85764, Germany

The modeling framework is being developed to complement the Wiki-style database of chemical structures available at http://qspr.eu (see also our presentation at CINF). It's main goal is to provide a flexible and expandable calculation environment, that would allow a user to create and manipulate QSAR and QSPR models on-line. The modeling framework is integrated with the database web-interface, that allows easy transfer of database data to the models. The web interface of the modeling environment is aimed to provide to the Web users easy means to create high-quality prediction models and estimate their accuracy of prediction and applicability domain. The developed models can be published on the Web and be accessed by other users to predict new molecules on-line. This tool is aimed to generate a new paradigm for structure activity relationship knowledgebases, making QSAR/QSPR models active, user-contributed and easily accessible for benchmarking, general use and educational purposes.

10:05 10 In silico profiling based on Aureus Global Pharmacology Space Knowledgebase
François Petitet, francois.petitet@aureus-pharma.com, Aureus Pharma, 174 Quai de Jemmapes, Paris, 75010, France

In the past years Aureus Pharma scientists assembled from structure-activity relationship literature a considerable amount of pharmacological data integrated into a unique knowledge management system. In Aureus Global Pharmacology Space (GPS) more than 500 000 chemical structures are linked to over 2 million quantitative biological activities for major therapeutic drug targets such as GPCRs, Kinases, Ion Channels, Proteases, and Nuclear receptors. Mining this GPS helps revealing potentially interesting polypharmacology compounds and rapidly generate in silico drug profiles based on chemical and biological annotations. Considering typical medicinal chemistry scaffolds such as phenothiazines, butyrophenones, benzodiazepines, dihydroperidines and others we analyzed the target activity profiles available for corresponding ligands and described in the GPS platform. For most of these structures we identified active representative compounds in several target protein classes. Using a newly developed application named AurPROFILER and thanks to our highly structured data schema and biological activities normalization, the target profiles obtained are easily visualized, analyzed, and reported. Several other examples of in silico generated profiles to build hypotheses on drug action mechanisms as well as off-target risk assessment will demonstrate the powerful approach of in silico profiling based on a strongly structured pharmacological knowledge database.

10:35   Intermission
10:50 11 BIDATA: An SAR Knowledgebase for data retrieval and new compound suggestions
Scott Oloff, Research Chemistry Systems, Boehringer-Ingelheim Pharmaceuticals Inc, 900 Ridgebury Road, PO Box 368, Ridgefield, CT 06877

Having a thorough understanding of the published SAR, internal data, and available IP is an absolutely necessity in the pharmaceutical industry. Many of these data sources however are scattered across multiple applications and in different formats making it difficult to interpret the data in the same context. This presentation will discuss approaches and technologies we have used to incorporate commercial SAR DB's with our own internal DB. There will also be discussions surrounding how this SAR is compared with patent DB's to identify available IP space.

11:20 12 Using knowledgebases of structure-activity-data, receptor-site and protein structural similarity to generate new matter ideas
Steven M Muskal, smuskal@eidogen-sertanty.com, Eidogen-Sertanty, Inc, 3460 Marron St #103-475, Oceanside, CA 92056

For several years, researchers have leveraged SAR, protein sequence and structural similarity in numerous ways, including but not limited to target hypothesis, target prioritization, ligand design, and lead optimization.

Strong synergies can be realized when coupling a large body of ligand-based structure-activity content with the growing body of target-based structural information. For example, given over 55,000 publicly available apo- and co-complex protein structures, very reliable models can be proliferated within and across many species. With this expanded structural view of the proteome, larger than expected conservation of receptor site-similarity can be identified and leveraged. We show how an automated design of novel matter by LigandCross or ligand hybridization using receptor-site similarity can be a very productive workflow.

1:30 37 Structure activity relationship analysis using PubChem
Evan Bolton, bolton@ncbi.nlm.nih.gov, National Center for Biotechnology Information, National Institutes of Health, 8600 Rockville Pike, Bethesda, MD 20894

PubChem is a free, online public information resource from the National Center for Biotechnology Information (NCBI). The system provides information on the biological properties and activities of chemical substances, linking together results from different sources on the basis of chemical structure and/or chemical structure similarity. With over 500 different targets, 1,400 bioassays, and 45,000,000 activity data points, PubChem is a significant source of publicly available bioactivity data. Unlike many available SAR Knowledgebases, PubChem contains screening data of both actives and inactives. Available tools allow one to dynamically create structure activity relationships based on structure similarity (2D or 3D), target similarity, and target profile. The use and utility of these tools will be discussed.

2:00 38 GOSTAR: GVK BIO online structure activity relationship database: Data and its utility
Jagarlapudi Sarma, sarma@gvkbio.com, Informatics, GVK Biosciences Private Limited, S-1, Phase-1, Industrial Technocrats Estate, Balanagar, Hyderabad, 500 037, India

GVK BIO is well known for the development of Knowledge databases of chemical entities (~4 million compounds) with structure activity relationships. Information relating chemical structure, biological target, in vitro and in vivo assay for efficacy/pharmacodynamics, clinical as well as Pharmacokinetics and toxicity is well integrated in different databases wherein the source information has been covered from a variety of Journals articles and patents for a variety of target families. Many pharmaceutical companies have been using these databases for different applications and/or modeling studies. Recently, GVKBIO has integrated all its individual databases into one single database, GOSTAR which has a very good web-based UI for different types of online queries. In the process of integration of all individual databases into one data model, all the data has been standardized and necessary taxonomy and ontology were used to handle the integrated data. Any query will extract the data from all databases whether they feature in discovery, development or marketed drug space. Further, one can analyze the retrieved molecules for any off-target activity as well as other indications. A number of descriptors can be generated using the online available tools and the data can be analyzed for various models. Tools have been developed to study and to visualize the chemical, biological and Therapeutic indication space as well as company related information. Further tools were developed to filter the data based on chemical, pharmacological or toxicity filters and help the research process for better drug discovery. We will be discussing some case studies on the usefulness of the database in the drug discovery.

2:30   Intermission
2:45 39 ChEMBL: Large-scale mapping of medicinal chemistry and pharmacology data to genomes
John P Overington, jpo@ebi.ac.uk, Team Leader, Chemogenomics and ChEMBL Databases, European Bioinformatics Institute, Wellcome Trust Genome Campus, Hinxton, CB10 1SD, United Kingdom

Although the majority of effective therapeutics are small molecules, there is relatively little readily accessible public domain data mapping drug to their molecular targets. When one considers clinical trial stage, or discovery stage data, the situation deteriorates further. However, this type of data is essential for Chemical Biology experiments, and is crucial for informed target selection in drug discovery. To address this issue, we have built a series of large scale databases, known as ChEMBL, that map small molecule structures to their target genes and also their functional effects. This data also captures a large ammount of human and model organism pharmacological data, systems often used in pre-clinical validation and safety pharmacology testing. A variety of applications of these databases in the area of target prioritisation, lead discovery, lead optimisation and drug repurposing will be described.

3:15 40 Pharmacoinformatics on very large annotated ligand databases
Rashmi Jain, rjain@evolvus.com and Aniket Ausekar, aniket@evolvus.com. Evolvus Group, 88, Shukrawar Peth, Prune, 411002, India

Ligand data excerpted, as a repository for past knowledge representation was prioritized. Accordingly, very large annotated ligand databases with more than 2 Million ligands, containing manual annotations on chemical and pharmacological data from Journals and Patents were used for mining compounds in an effort to identify de-novo candidates in a virtual screen, against selected, previously validated targets. Clustering on controlled datapoints against all major therapeutically relevant target families (GPCR, Ion-channel, Protease, Transporters, Kinase, Nuclear Hormone receptor) was performed and challenging compounds were designed. Designed compounds represented an unique set of chemistry and were synthesized for further validation.


HIST - Classic Books in Chemistry VI: The Language of Chemistry
Washington Plaza Franklin Room
Organized by: James J. Bohning, Ned D. Heindel
Presiding: Ned D. Heindel, Ronald S. Brashear
9:00   Introductory Remarks
9:05 1 Austin M. Patterson: Words About Words and his contributions to nomenclature
John B Sharkey, jsharkey@pace.edu, Department of Chemistry and Physical Sciences, Pace University, Pace Plaza, New York, NY 10038

Early in his long and distinguished career (1876-1956), Austin Patterson recognized the significant, ever-growing need for a better language of chemistry, and he went to work to help in providing such a language. He virtually devoted his life to the development of chemical nomenclature and to fostering good usage. He became widely recognized as the world's leading authority in this field. Perhaps the culmination of his life's work, undertaken during the last five years of his life, was the writing of a regular column in Chemical and Engineering News. This column, entitled “Words about Words” in the beginning and later just labeled “Nomenclature,” was widely read. In 1957, the ACS published e reproduction of his columns. According to E. J. Crane, who wrote the Preface, “This book is produced for use, but it is also offered for memory and for inspiration.” This paper will highlight Patterson's contributions to the field of nomenclature and review some of his more interesting columns.

9:35 2 Metaphorical matter: The language of alchemy
Anke Timmermann, Chemical Heritage Foundation, 315 Chestnut Street, Philadelphia, PA 19106

Alchemists wrote down their experiments, theories and observations in their own way long before the concepts of atoms and molecules, chemical formulae and reactions were articulated in the images and formulae familiar to us today. The practice and theory of alchemy were rooted in ancient traditions which had come to the Western world from Egypt, ancient Greece and the Islamic countries. It was believed that the convoluted language of alchemical writings could only be deciphered by initiated alchemists. Altogether, the language of alchemy provides a rather intriguing combination of alchemical information and symbolic expression. How, then, was it possible for alchemists to communicate practical and theoretical knowledge? This talk will discuss alchemy and its symbols with the help of examples (word and image) from the rare book collections in the Othmer Library.

10:05 3 Méthode de Nomenclature Chimique revisited
Carmen J. Giunta, giunta@lemoyne.edu, Department of Chemistry and Physics, Le Moyne College, 1419 Salt Springs Rd, Syracuse, NY 13214-1399

The Méthode de Nomenclature Chimique, published in 1787, provided the basis for the systematic nomenclature of binary inorganic compounds still in common use more than two centuries later. The presentation will examine the component parts of this publication, particularly Lavoisier's memoir that advocated reforming and perfecting chemical nomenclature, Guyton de Morveau's memoir on developing the principles of the proposed systematic nomenclature, and glossaries of chemical names old and new.

10:35   Intermission
10:45 4 Documenting the history of chemical nomenclature and symbolism
William B. Jensen, jensenwb@email.uc.edu, Department of Chemistry, University of Cincinnati, ML 172, Cincinnati, OH 45221-0172

The talk will review attempts by past chemical historians to document the history of chemical nomenclature and symbolism, ranging from coverage in standard histories of chemistry, such as those by Kopp and by Ihde, to specialized monographs, such as those by Caven and Cranston and by Crosland.

11:30 5 Systematizing chemical nomenclature: IUPAC's Red Book and Blue Book
Roger A. Egolf, rae4@psu.edu, Pennsylvania State University, Lehigh Valley Campus, 8380 Mohr Lane, Fogelsville, PA 18051-9999

One of the original purposes of the International Union of Pure and Applied Chemistry at it foundation in 1919 was the unification of chemical nomenclature. Commissions of IUPAC published reports suggesting standardized nomenclature over many years, but it was not until 1955 that tentative rules for inorganic and organic nomenclature were published in Comptes Rendus. These rules were ratified at the 19th IUPAC Conference in 1957, then published as Nomenclature of Inorganic Chemistry – 1957, better known as the Red Book; and Nomenclature of Organic Chemistry – 1957, Section A Hydrocarbons, and Section B Fundamental Heterocyclic Systems, better known as the Blue Book. This paper will discuss the process by which these rules were agreed upon and published.

12:00   Lunch Break
2:00 6 What's in a name?
Natalie Foster, nf00@lehigh.edu, Department of Chemistry, Lehigh University, 6 East Packer Ave, Bethlehem, PA 18015

“Organic Chemistry: The Name Game” is a good-humored text that explores the origins of contemporary terms in organic chemistry. The forward to this little gem of a book reminds us that in science, just as in literature, “language does not serve mankind only for communication any more than food serves only for nourishment.” This paper presents a selection of the stories behind the trivial names that are part of the language of organic compounds and chemical concepts. This excursion through the origin of names coined with reference to animals (felicene), architectural elements (peristylane), musical instruments (fidecene), food (sandwich compounds), and even head-coverings (diademane) illuminates the human side of chemistry highlights the strong links between words and pictures (names and shapes) that describe how chemists view the world.

2:30 7 mmCIF: A computer language for the representation of macromolecular structure
Julie B. Ealy, jbe10@psu.edu, Department of Chemistry, Pennsylvania State University, 8380 Mohr Lane, Academic Building, Fogelsville, PA 18051

The language of the macromolecular crystallographic information file will be described as presented in: Bourne, P. E., Berman, H. M., McMahon, B., Watenpaugh, K. D., Westbrook, J. D., and Fitzgerald, P. M. D. Methods in Enzymology, 1997, 277, 571-590. The language was developed to extend the Crystallographic Information File (CIF) data representation that is used to describe molecular structure. Visually, aspects of the Protein Data Bank will used to demonstrate various aspects of the language.

3:00   Intermission
3:10 8 Putting it on the line: The Wiswesser line-formula notation system (WLN)
James J. Bohning, jjba@lehigh.edu and Ned Heindel. Department of Chemistry, Lehigh University, 6 E. Packer Ave, Bethlehem, PA 18015

The effort to reduce chemical structures of any complexity to a single line of letters, numbers and symbols began in the eighteenth century, but did not receive serious attention until the early computer age when in 1949 the IUPAC Commission on Codification, Ciphering, and Punched Card Techniques invited designers to submit their proposals for an internationally suitable notation system. Although IUPAC selected a system developed by G. M. Dyson, it was the WLN that won the most users, primarily through the determined efforts of its founder, William J. Wiswesser, who outlined the principles of the WLN in his 1954 monograph "A Line-Formula Chemical Notation." As Wiswesser explained, the WLN never enjoyed any IUPAC recognition, and had no other official approval. It earned user support “simply because it solved various information-managing needs with less cost and confusion than other internationally recognized alternatives.”

3:55 9 CAS REGISTRY: Its history and principles
Roger J. Schenck, Chemical Abstracts Service, 2540 Olentangy River Road, Columbus, OH 43202

The CAS REGISTRYSM is the master collection of disclosed chemical substance information, with more than 45 million organic and inorganic molecules. This talk will focus on the nature of the CAS REGISTRY® Number as a unique identifier, and the principles and criteria for substances being added to the CAS REGISTRY. Examples will be given illustrating the breadth and depth of the CAS REGISTRY.


COMP - Structure Activity Relationship Knowledgebases
Walter E. Washington Convention Center 147 A
Organized by: Evan Bolton, Stefan Senger
9:00 67 Linking genomic knowledge to natural products and drugs
Minoru Kanehisa, kanehisa@kuicr.kyoto-u.ac.jp, Bioinformatics Center, Institute for Chemical Research, Kyoto University, Gokasho, Uji, Kyoto, 611-0011, Japan

The large-scale datasets generated by genome sequencing and other high-throughput experimental technologies are the basis for understanding life as a molecular system and for developing medical, pharmaceutical, and other practical applications. The key to linking such large-scale datasets to practical values lies in bioinformatics technologies, not only in terms of computational methods, but also in terms of knowledge bases. In the KEGG database resource (http://www.genome.jp/kegg/) we organize our knowledge on higher-level systemic functions in computable forms, such as metabolism in KEGG pathway maps and therapeutic category of drugs in BRITE functional hierarchies. This enables bioinformatics analysis of genomic and molecular-level data to infer higher-level functions through the process of pathway mapping and BRITE mapping. A variant of this approach is to infer chemical structures of endogenous molecules that can be synthesized in a given organism, knowing the enzyme repertoire in the genome and the biosynthetic pathways, together with possible biological activities. I will report on our strategy to analyze the chemical architecture of natural products derived from enzymatic reactions (and enzyme genes) and the chemical architecture of marketed drugs derived from human made organic reactions in the history of drug development.

9:30 68 Metabolic liability and SAR analyses derived from bioactivity databases
Russ Hillard, russ.hillard@symyx.com, Product Marketing, Symyx Technologies inc, 2440 Camino Ramon, San Ramon, CA 94583

SAR analyses conducted on libraries taken from bioactivity databases can yield insight into the dependence of therapeutic activity (and/or adverse side effects) on variations in chemical structure. Often such studies make the assumption that administered compounds are, in fact, the active chemical agents. Metabolic transformations following administration but prior to key biochemical processes involved in observed activity can produce significant structural modifications in the actual bioactive entities. Ideally, then, SAR analyses should include examination of known metabolic outcomes for compounds under investigation. Mining this information from available electronic collections of known biotransformations and correlating it to SAR data will be discussed.

10:00   Intermission
10:15 69 Discovery and data mining using the NCBI BioSystems database, a centralized repository linking small molecules to their biological function
Lewis Geer, lewisg@ncbi.nlm.nih.gov, National Center for Biotechnology Information, Bldg. 38A, Room 5S512, 8600 Rockville Pike, Bethesda, MD 20894

The NCBI BioSystems database contains biological relationships between the small molecule records found in PubChem and the gene and protein records found in Genbank. These relationships directly link the structure of small molecules to their biological function. By centralizing and standardizing these records and then linking them to multiple NCBI databases like PubMed and PubChem BioAssay, the BioSystems database is intended to be a convenient and extensive resource for fundamental structure-function information and associated annotations.

10:45 70 SAR studies using ChemBiobase, a knowledgebase on Target centric small molecules
Sooriya Kumar, sooriya_kumar@jubilantbiosys.com, Jubilant Biosys, # 96, 2nd Stage Industrial Suburb, Yeshwantpur, Bangalore, 560 022, India

Scientists involved in drug discovery process require broad range of information to assist their decision making process. To help in this task, they have access to large databases built in-house as well as provided by various vendors. In addition, they refer to vast amount of scattered information available as Patent and Journal literature. They further look for solutions which help to manage the data deluge. Given this, Jubilant has developed comprehensive set of target centric ligand databases i.e. ChemBioBase which provide useful and important complimentary information on small molecules that exhibit activity against targets in a particular family. These databases cover wide range of druggable targets including Kinases, Proteases, GPCR's, Ion channels and Nuclear Hormone receptors. Such thematic databases would help the researchers to know everything in the given field and carry out several virtual screening tasks. ChemBioBase would allow the researchers to perform structure-activity relationship (SAR) studies for molecules tested for a particular target at a given assay condition across the publications. Manually drawn chemical structures from ChemBioBase are used for clustering of molecules. This is done with respect to defined scaffold or activity and to create chemical libraries. Utility of these databases towards SAR along with content and coverage in terms of chemistry/biology spaces will be discussed.

11:15   Panel Discussion


SCHB - Leveraging the Internet to Advance your Position in the Market
Washington Plaza Jefferson Room
Organized by: Joseph E. Sabol
1:30   Introductory Remarks
1:35 5 Navigating social networking and collaboration tools
Christine Brennan Schmidt, c_schmidt@acs.org, Web Strategy & Operations, American Chemical Society, 1155 Sixteenth Street, NW, Washington, DC 20036

The popularity of social networking and online collaboration tools is growing rapidly. The use of these tools, including LinkedIn, Yammer, Plaxo, and CollectiveX, in the professional world is becoming more common. Even the purely networking sites such as Facebook and Twitter are finding business use. Among these tools is the ACS Network, released in 2008. Learn more about various existing social networking and collaboration tools, the features they have, their differences and overlaps in functionality, and the activities they support. Hear about the current and future offerings of the ACS Network.

2:05 6 Growing your chemical business? Let SciFinder be part of the process!
Marsha J. Davenport, mdavenport@cas.org, Chemical Abstracts Service, 12525 Plantation Drive, Brandywine, MD 20613

SciFinder, Chemical Abstract Service's computerized literature searching system, is now web-based! With SciFinder you can explore one single source for scientific information in journal and patent literature from around the world with new browser-based searching capabilities. This presentation will review the changing face of SciFinder, with the goal of familiarizing attendees with its new functionality.

2:35 7 Finding gold: Using internet resources to help make good business decisions
Anne Caputo, Special Libraries Association, 1025 Connecticut Avenue, NW, Suite 1103, Washington, DC 20036

The Internet provides access to a myriad of business resources useful to small businesses. Business directories, catalogs of specialized suppliers, market and competitive intelligence sources, and global business opportunities are the special resources used daily by information professionals in specialized libraries and information centers. Learn about the sources and methods used by these skilled professionals which translate into tools and opportunities for small businesses. Practical tools and search techniques feature access to Internet-based sources offering the greatest value to those wishing to maximize the potential of web content for business development and management.

3:05   Intermission
3:15 8 ChemSpider: Building a knowledge-based community for chemists using social and data networking technologies
A. Williams, antony.williams@chemspider.com, ChemZoo Inc, 904 Tamaras Circle, Wake Forest, NC 27587

In less than 2 years ChemSpider has become one of the primary online resources for chemists providing access to an unsurpassed aggregate of free-access knowledge and data. ChemSpider was developed with the intention of providing a structure centric community for chemists that would be enhanced by data depositions, curations and annotations by the community. The system presently hosts over 21.5 million chemical compounds from over 200 data sources. Working with a network of advisors, collaborators and data providers ChemSpider has created a unique resource of integrated information for chemists. These efforts have enabled us to support the curation of the Wikipedia chemistry pages, the production of a community supported Open Access chemistry journal and provision of web services integrated to spectrometer systems distributed around the world. This talk will provide an overview of how ChemSpider utilized social and data networking to create a community for chemistry.

3:45 9 The "design approach" to creating effective websites
Mark D. Carpenter, M_Carpenter@acs.org, Web Strategy and Operations, American Chemical Society, Washington, DC 20036

Designing and maintaining a customer friendly web site is crucial to any small business success, as nearly all customers are relying on the Internet to find information about the companies they do business with and the products and services they buy. This presentation will explore how ACS uses customer feedback to build user centric web experiences that enable members to get information quickly and easily. Other examples of the best practices for building successful and engaging web sites will be presented, so that small and growing businesses can increase their exposure in the crowded Internet.

4:15 10 Effective use of the Internet to improve market share, drive sales, and increase customer loyalty
Aaron R. Warner, awarner@idtdna.com, Integrated DNA Technologies, Inc, 1710 Commercial Park Rd., Coralville, IA 52241

This presentation will reveal unorthodox marketing methods that have been used to gain market share; the principles and technologies that have helped streamline a complex design and ordering process; and the systems that have been assembled to calculate the return on investment for the marketing and ordering tools. IDT has employed a unique mix of custom applications and third-party tools to exceed the expectations of customers before, during, and after orders are placed. Topics presented will include IDT's no-charge bioinformatics offerings, the use of search engines, external integration methods, and internal software development. For each, discussion will focus on what has worked, what has not, and reasons why. IDT is a custom manufacturer of synthetic oligonucleotides and genes for the research and diagnostic markets, with over 80,000 active customers worldwide, and accepts more than 85% of it's orders through its website.

4:45   Concluding Remarks


COMP - Molecular Visualization: small molecules, BIG IMPACT
Walter E. Washington Convention Center 145 B
8:00   Introductory Remarks
8:05 146 Visualization of cyclic and multibranched molecules with VMD
Simon Cross, hodgestar@gmail.com1, John E. Stone, johns@ks.uiuc.edu2, James E. Gain1, and Michelle M. Kuttel, mkuttel@cs.uct.ac.za1. (1) Department of Computer Science, University of Cape Town, Private Bag X3, Rondebosch, Cape Town, 7701, South Africa, (2) Beckman Intitute, University of Illinois at Urbana-Champaign, 405 N. Mathews Ave., Urbana, IL 61801

We have added two new visualization algorithms, termed PaperChain and Twister, to the Visual Molecular Dynamics (VMD) package. These algorithms produce visualizations of complex cyclic and multi-branched molecular structures. PaperChain highlights each ring in a molecular structure with a polygon, which is coloured according to the ring pucker. Twister traces the glycosidic backbone with a ribbon that twists according to the relative orientation of successive sugar residues. Combination of these novel algorithms with the large set of visualizations already available in VMD allows for unprecedented flexibility in the level of detail displayed for glycoproteins, as well as other cyclic structures. We highlight the efficacy of these algorithms with selected illustrative examples, clearly demonstrating the value of the new visualizations, not only for structure validation, but for facilitating insights into molecular structure and mechanism.

8:40 147 PoseView: 2D Visualization of protein-ligand complexes
Katrin Stierand, stierand@zbh.uni-hamburg.de, Center for Bioinformatics, University of Hamburg, Bundesstr. 43, Hamburg, 20146, Germany and Matthias Rarey, Center for Bioinformatics (ZBH), University of Hamburg, Bundesstrasse 43, 20146 Hamburg, Germany.

Although computer-aided molecular design and virtual screening software tools improve continuously, manual investigation of the resulting complexes a control task in modelling. In contrast to 3D visualization, information contained in 2D plots can be identified by a short glance and are therefore more appropriate for scanning through large datasets.

We present a new version of PoseView,[1,2] a computational method for the automatic generation of two-dimensional protein-ligand complex diagrams. The layout is computed considering hydrophilic, hydrophobic and metal contacts between ligand and receptor. While the ligand and protein residues forming hydrophilic interactions to the ligand are drawn according to chemical structure diagram conventions, the hydrophobic contacts are visualized by means of splines around the ligand and the appropriate residue labels. PoseView is based on a combinatorial layout optimization strategy which solves parts of the problem non-heuristically. The computation is performed in a sequential manner: An initial ligand structure diagram is created and subsequently modified in order to find a non-intersecting arrangement of interaction lines. In the following the initial placement of each hydrophilic interacting amino acid is computed. During the placement collisions are resolved by a branch & bound algorithm selecting an optimal relative arrangement of all amino acids and the ligand. Finally, the remaining components of the complex diagram are placed based on an underlying arrangement grid.

For validation, PoseView was applied to the protein-ligand complexes contained in the Brookhaven PDB database. Advantages and limitations of the approach will be discussed by means of representative test cases.

For examples see www.zbh.uni-hamburg.de/poseview


1.Stierand, K., Maaß, P., Rarey, M. (2006) Molecular Complexes at a Glance: Automated Generation of two-dimensional Complex Diagrams. Bioinformatics, 22, 1710-1716.

2.Stierand, K., Rarey, M. (2007). From Modeling to Medicinal Chemistry: Automatic Generation of Two-Dimensional Complex Diagrams. ChemMedChem 2, 6, 853-860.

9:15 148 A general interface to quantum chemistry simulations in VMD
Jan Saam, saam@ks.uiuc.edu1, John E. Stone, johns@ks.uiuc.edu2, Axel Kohlmeyer, akohlmey@cmm.chem.upenn.edu3, and Klaus Schulten, kschulte@ks.uiuc.edu1. (1) Beckman Institute, University of Illinois at Urbana-Champaign, 405 N. Mathews Ave., Urbana, IL 61801, (2) Beckman Intitute, University of Illinois at Urbana-Champaign, 405 N. Mathews Ave., Urbana, IL 61801, (3) Center for Molecular Modeling, Chemistry Department, University of Pennsylvania, 231 South 34th Street, Philadelphia, PA 19104

We describe our efforts in supporting quantum chemistry data in the VMD software package. VMD has long been used for visualization and analysis of classical molecular dynamics simulations, but representation of results from quantum chemistry software was limited to coordinates or precomputed orbital grids (e.g. cube files). Recent advances in the use of multi-core processors and massively parallel graphics processor provided an opportunity for truly interactive dynamic trajectory visualization of orbitals, the molecular electrostatic potential, etc. In combination with VMD's other powerful graphics capabilities this lays a foundation for new visualization paradigms for quantum chemistry data appealing to the chemist's intuition. Further, arbitrary postprocessing and analysis steps can be applied interactively or through scripting. New extensions to the VMD plugin interfaces allow the easy import of various data from a wide variety of quantum chemistry packages into VMD. Additional plugins assist in generating input for quantum chemical calculations.

9:50   Intermission
10:00 149 Boltzmann 3D simulations for visualizing molecular motion in the classroom and laboratory
Randall B. Shirts, randy_shirts@byu.edu, Department of Chemistry and Biochemistry, Brigham Young University, C100 Benson Building, Provo, UT 84602

In addition to visualization of chemical structures, computers can also help in visualizing molecular motion. In particular, the distribution of molecular velocities is an essential concept in understanding gas laws, rates of diffusion and effusion, rates of evaporation, rates of chemical reaction, and the nature of equilibrium. Boltzmann 3D is a free Java application available at http://people.chem.byu.edu/rbshirts/research/boltzmann_3d that performs real-time simulation of hard spheres for classroom demonstrations or hands-on interactive laboratories from high school chemistry to graduate statistical mechanics. I will demonstrate the capabilities of this freeware including new modules for doing isothermal or adiabatic expansions/compressions and for kinetics and equilibrium.

10:35 150 Visualization of molecular orbitals and the related electron densities
Maciej Haranczyk, mharanczyk@lbl.gov1, Gunther Weber1, and Maciej S J Gutowski, m.gutowski@hw.ac.uk2. (1) Computational Research Division, Lawrence Berkeley National Laboratory, One Cyclotron Road, Mail Stop 50F-1650, Berkeley, CA 94720, (2) Chemistry-School of Engineering and Physical Sciences, Heriot-Watt University, William H Perkin Building, Edinburgh EH14 4AS, United Kingdom

When plotting different molecular orbitals and the related electron densities with consistent contour values, one can create illusions about the relative extension of charge distributions. We have recently suggested that the comparison is not biased when plots reproduce the same fraction of the total charge. We developed an algorithm and software that facilitate this type of visualization. This presentation will illustrate the application of our tools in the analysis of molecular orbitals, the related electron densities, and the total electron densities of molecules. In addition, we will present approaches that can be useful in the analysis of the electron density fields but they have not yet been implemented in the mainstream visualization packages. An example of such approaches is the field topology analysis using contour trees representations.

This work is supported by the U.S. Department of Energy under Contract No. DE-AC02-05CH11231.

11:10 151 Molekel: A program for the visualization of quantum chemistry data
Ugo Varetto, uvaretto@cscs.ch, Maria G. Giuffreda, mgg@cscs.ch, and Yun Jang, jangy@cscs.ch. Swiss National Supercomputing Centre - CSCS, Galleria 2 - Via Cantonale, Manno, 6928, Switzerland

Molekel is a multi-platform open-source molecular visualization program that can display 3-D models of chemical structures as well as the results of quantum chemistry computations. The presentation gives an overview of the main program features with a focus on the visualization and analysis of data read from the output of popular quantum chemistry packages such as ADF, Gaussian and GAMESS. The final part of the presentation covers the new hardware-accelerated visualization techniques available in future versions of Molekel which are used to enhance depth perception of 3-D structures and achieve very fast and high-quality display of electron density and molecular orbitals.

11:45 152 WebMO: Web-based, state-of-the-art, and cost effective computational chemistry
William F. Polik, Department of Chemistry, Hope College, 35 E. 12th Street, Holland, MI 49423 and Jordan R. Schmidt, Department of Chemistry, University of Wisconsin - Madison, Madison, WI 53706.

WebMO is a web-based interface to modern computational chemistry programs (GAMESS, Gaussian, Molpro, MOPAC, NWChem, PQS, Q-Chem). Using just a web-browser, users can draw 3-D structures, run calculations, and visualize results. WebMO is simple enough for novice users (reasonable defaults are provided; result are presented graphically) but flexible enough for experts (full access to input and output files is provided; templates allow customization of calculation types). WebMO is ideal for teaching at the undergraduate and graduate levels, for research students learning and using computational chemistry, and for creating input files and visualizing computed results.


COMP - Molecular Visualization: Giving Your Proteins Appeal
Walter E. Washington Convention Center 146 B
Organized by: Rommie E Amaro, Emilio Xavier Esposito
8:00   Introductory Remarks
8:05 298 Use of quaternions in biomolecular structure analysis
Robert M. Hanson Daniel Kohler, Steven Braun
8:40 299 Sirius: A versatile desktop visualization environment
Anne Bowen Oleksandr Buzko, Kim Baldridge
9:15   Intermission
9:25 300 Molecular visualization and animations using PMV
Michel F. Sanner
10:00 301 UCSF Chimera
Thomas Ferrin Conrad C. Huang, Thomas D. Goddard, Eric F. Pettersen, Gregory S. Couch, Elaine C. Meng
10:35 302 PyMOL molecular viewer: Updates and refinements
Warren L DeLano




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