erice 2008 introduction to pdb workshop from molecules to medicine: integrating crystallography in...
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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 Bank50 thousand served
Protein Data Bank50 thousand served
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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 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 RemediationBefore 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?
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
OMIMGenomes(NCBI Gene)
SG TargetsLiterature
NCBITaxonomy
Type of InformationExternal Data (Integrated)
Current Status of Data IntegrationNAR 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
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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) 6:21.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 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
AcknowledgementsOperated by two
members of the RCSB:
Supported by:
NIGMS
The RCSB PDB is a member of the