Erice 2008 Introduction to PDB Workshop From Molecules to Medicine: Integrating Crystallography in Drug Discovery Erice, 29 May - 8 June Peter Rose University of California San Diego

Erice 2008 Vision To provide a global resource for the advancement of research and education in biology and medicine by curating, integrating, and disseminating biological macromolecular structural information in the context of function, biological processes, evolution, pathways and disease states. We will implement standards, and anticipate and develop appropriate technologies to support evolving science.

Erice 2008 Organization  wwPDB  RCSB PDB, PDBj, MSD-EBI, BMRB  Ensures a single worldwide archive of biological macromolecular structure data  One member is the archive keeper (RCSB PDB)  RCSB  Rutgers, UCSD

Erice 2008 Number of released entries Year: 2008 Protein Data Bank 50 thousand served Protein Data Bank 50 thousand served

Erice 2008 Structure Deposition and Dissemination

Erice 2008 Data Remediation  Sequence  Resolved anomalies relative to UniProt (61K sequences)  Resolved anomalies between chemical sequence and atomic sequence  Ligands and monomers  New dictionary with full chemical description (now definitions)  All files annotated relative to this dictionary (163K non-polymers + 23M polymer residues)  Biological assembly defined  Viruses now uniformly annotated (~280 entries)  Atom nomenclature  Conforms to IUPAC

Erice 2008 Virus Structure Remediation BeforeAfter

Erice 2008 Topics of PDB Workshop: Focus on Drug Discovery  How to find a target protein or related proteins?  What is the biologically relevant unit?  How to find structures with bound ligands?  How to view structures and protein-ligand interactions?  How to create datasets for comparative analysis?

Erice 2008 Current State of Data Query  Intelligent keyword searches of structure data and web pages  Advanced iterative searches across many types of data  Browsing via tree structures  Search by sequence, chemical structure, function, genome location, etc.  Query by example – Part of the result from one query can immediately be used as a new query

PDB UniProt Gene Ontology Organism OMIM Genomes (NCBI Gene) SG Targets Literature NCBI Taxonomy Type of Information External Data (Integrated) Current Status of Data Integration NAR 2005, 33: D233-D237 RCSB PDB Managed Resource Sequence Structure Function Disease SCOP/CATH BioCyc Pfam Reactome Enzyme Classification PubMed GeneRIF IHOP Abstract search Display Keyword search Browse Detailed search Ensembl Sequence-structure mapping dbSNP Superdrug (Link) Many more... Superfamily NDB

Erice 2008 Current Data Result Display  Tabular reports  Sequence alignments  Molecular interactions  Histograms  Graphical distributions  Collages

Erice 2008 Current Status of Web Visualization Tools  Common visualization tools e.g., Jmol, KiNG, WebMol, QuickPDB  Specific applications for views of specific data types using a common framework (MBT)  Protein Workshop (publications)  Simple Viewer (large complexes)  Ligand Viewer (pharmacology) See BMC Bioinformatics (2005) 6:21. Funded in part by NIH GM63208

Erice 2008 Ligand Centric Features  Powerful ligand-based query and retrieval  Based on remediated ligand data  Ligand-centric view of search and display  Ligand data download  Display of detailed interactions– requires no understanding of a molecular viewer  BindingDB – literature curated binding affinities (with Prof. Gilson)  Links to Super Drug Database

Erice 2008 RCSB PDB – BindingDB Linkages Link by PDB ID Ligand similarity search Link by ligand IDLink by PDB ID

Erice 2008 Acknowledgements Operated by two members of the RCSB: Supported by: NIGMS The RCSB PDB is a member of the