PubChem: An Open Repository for Chemical Structure and Biological Activity Information Steve Bryant The NIH Biowulf Cluster: 10 Years of Scientific Supercomputing February 3, 2009 NIH Molecular Libraries Basic design / approach Current discovery tools / example Planned discover tools New discovery tools ? PubChem Overview NIH Molecular Libraries Program Molecular Libraries Screening Centers Network (MLSCN) Compound Repository (MLSMR) Instrumentation Chemical Diversity Assay Development Predictive ADMET Technology Development Screening Informatics Cheminformatics Research Centers Molecular Libraries BioAssays Investigator Customized Assay Screen Hit picking, confirmation, secondary screens Hit List Optimization Chemistry Compound Repository Assay Peer review Molecular Libraries Components MLSCN Created 2005 MLPCN Created 2008 NIH Molecular Libraries overview Basic design / approach Current discovery tools / example Planned discover tools New discovery tools ? PubChem Overview GenBank model direct depositions by investigators highly automated (low database cost) 25 year precedents in biology less precedent in chemical biology PubChem Approach Growth In PubChem Contributing Organizations Contributed substance records with chemical structure chemical names and comments links to contributor web sites contributed links to other NCBI biomedical databases PubChem Contents Growth In PubChem Substances / Compounds PubChem Standardization... Contributed bioassay records with assay description / protocol links to tested substances summary and detailed test results links to contributor web sites and other NCBI databases PubChem Contents Growth In PubChem BioAssays Growth In PubChem Tested Substances NIH Molecular Libraries overview Basic design / approach Current discovery tools / example Planned discover tools New discovery tools ? PubChem Overview Optimize discoverability for molecular biologists by integrating PubChem into NCBIs Entrez / PubMed Search Engine Chemical structure search Bioassay result search Structure-activity tools PubChem Retrieval System NCBIs Entrez Search Engine... Entrez Links and Neighbors... Protein Sequences Protein 3D Structure Activity Profile Similarity PubChem Small Molecules PubMed Literature Bioactivity Screens VAST Structure Similarity Term Frequency Statistics Chemical Structure Similarity 2,000,000 users... 60,000,000 hits... per day Target Sequence Similarity PubChem Users per Day Search for Shoichet inhibitors... PubMed Article Retrieved... Link to PubChem Records... Kaempferol in PubChem... Similar Compounds in PubChem... Quercetin in PubChem... Compare Protein / Ligand Complexes... Link to Another Structure... Tyrosine Kinase Family Member... Links from Quercetin to PubMed... PubMed Records... Links from Quercetin to BioAssays... BioAssay records... BioAssay where Active... Entrez Links and Neighbors... Protein Sequences Protein 3D Structure Activity Profile Similarity PubChem Small Molecules PubMed Literature Bioactivity Screens VAST Structure Similarity Term Frequency Statistics Chemical Structure Similarity 2,000,000 users... 60,000,000 hits... per day Target Sequence Similarity Optimize discoverability for molecular biologists by integrating PubChem into NCBIs Entrez / PubMed Search Engine Chemical structure search Bioassay result search Exploratory structure-activity tools PubChem Retrieval System Compounds Similar to Quercetin... PubChem Bioactivity Analysis... PubChem Structure-Activity... Active Compound Cluster... BioAsay Cluster... Another BioAssay Cluster... PubMed Connection... PubChem Structure-Activity... NIH Molecular Libraries overview Basic design / approach Current discovery tools / example Planned discover tools New discovery tools ? PubChem Overview Bottom-line Summaries of multi-step Molecular Libraries screens Chemical Reagent links for gene and protein records when possible Add 3D-conformer similarity to structure-activity analysis Support multi-target panel screens Planned Discovery Tools Quercetin in PubChem... Quercetin Similar Conformers... NIH Molecular Libraries overview Basic design / approach Current discovery tools / example Planned discover tools New discovery tools ? PubChem Overview Systems-biology pathway links among chemical biology screens / results Links to bioactivity information derived from scientific literature, literature abstraction, and other sources New Discovery Tools ? Quercetin in PubChem... Quercetin NLM Toxicology... Quercetin NLM Toxicity... Evan Bolton Jie Chen Svetlana Dracheva Lewis Geer Lianyi Han Jane He Siqian He Karen Karapetian Vahan Simonyan Ben Shoemaker Wenyao Shi Tugba Suzek Paul Thiessen Valery Tkachenko Jiyao Wang Yanli Wang Jewen Xiao Jian Zhang