Introduction to PDB Workshop From Molecules to Medicine: Integrating Crystallography in Drug Discove

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Introduction to PDB WorkshopFrom Molecules to
Medicine Integrating Crystallography in Drug
Discovery Erice, 29 May - 8 June

• Peter Rose
• pwrose_at_ucsd.edu
• University of California San Diego

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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.

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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

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Protein Data Bank 50 thousand served
Number of released entries
Year
2008
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Structure Deposition and Dissemination
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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 8650 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

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Virus Structure Remediation
Before
After
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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?

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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

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Current Status of Data Integration
NAR 2005, 33 D233-D237
UniProt
PubMed

• Sequence-structure
• mapping

GeneRIF
Literature
PDB
SG Targets

• Abstract search
• Display

• Keyword search
• Browse
• Detailed search

IHOP
Disease
Organism
Sequence
Structure
Function
NCBI Taxonomy
Genomes (NCBI Gene)
SCOP/CATH
BioCyc
OMIM
Reactome
dbSNP
Superfamily
Ensembl
Gene Ontology
Superdrug
NDB
Pfam
Type of Information
Many more...
Enzyme Classification
External Data (Integrated)
(Link)
RCSB PDB Managed Resource
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Current Data Result Display

• Tabular reports
• Sequence alignments
• Molecular interactions
• Histograms
• Graphical distributions
• Collages

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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) 621. Funded in
part by NIH GM63208
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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 interactionsrequires no
  understanding of a molecular viewer
• BindingDB literature curated binding affinities
  (with Prof. Gilson)
• Links to Super Drug Database

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RCSB PDB BindingDB Linkages
Link by PDB ID
Link by ligand ID
Link by PDB ID
Ligand similarity search
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Acknowledgements
Operated by two members of the RCSB
The RCSB PDB is a member of the
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