Macromolecular Structure Database group

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MSDsite
PDB ligand environment
www.ebi.ac.uk/msd-srv/msdsite
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Introduction

• Many protein (and some nucleic acids) structures
  have evolved as a framework for an active site
  where chemistry takes place.
• The active site is critical for the understanding
  the action of proteins and their role within the
  cell mechanism.
• The function, of these macromolecules can best be
  studied by detailed 3-dimensional knowledge of
  these active sites.
• Because the active site is a local 3D environment.

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Ligand environment

• The 3D / 1D position that defines the protein
  function
• disparate amino acids on the 1D sequence
• A localized volume in 3D
• Where chemistry/binding happens.

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MSD site database

• The MSD site database contains local structural
  information around all the bound ligands within
  the PDB
• All proteins deposited to the PDB are checked for
  ligand(s). These are HETATM non-protein/non-nuc
  leic-acid/non-water residues.
• Interactions are stored within the DB
• The bound ligand coordinates associated
  information
• The ligand environment (i.e. any residue that
  interacts)
• The interaction types between the ligand and
  environment.
• All sequences are checked for the registered
  ProSite patterns and matches are stored in the DB
• Fast algorithm for a pattern search is embedded
  into the DB

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Site definitions

• Sites are defined as a ligand environment when a
  ligand is presented.
• Sequence motifs matching is applied for site
  definition independently from ligands.
• ProSite sites
• http//www.expasy.org/prosite
• Catalytic sites atlas http//www.ebi.ac.uk/thor
  nton-srv/databases/CSA/
• Merops active sites
• http//merops.sanger.ac.uk/

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Environment
Ligand environment analysis
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Possible site searches

• Define search by ligand
• Define search by sequence motif (pattern)
• Define search by metal site geometry
• Define search by environment
• has same environment
• has similar environment

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MSDsite interface
Query editor
Filters
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Query generation
HISSERS/HgtC2.0 HIS.NE2S/SgtC2.0 HIS.N/TgtC2.0
Drawing Complex queries secondary
structure Distance cut-offs Bond type Side/main
chain
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Search service aims

• Form a site search criteria
• Provide a hit list
• Visualize the found sites
• XML technology (xpath,..) to search an XML
  corresponding to a PDB entry from the hit list.

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Example
Pattern is defined as HIS-any-HIS-GLU
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Hit List Help
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Hit List Visualization tools
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Searched site visualization
AstexViewertm Groups menu
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Hit List Link to Details
Bound molecules form
Sequence from
Atomic bonds
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Detail forms header
Links to the other views of the same PDB entry
Ligand binding statistics
Switch on/off undefined bonds
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Sequence form
Show site
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Bound molecules form
Ligands that match a search creteria
Environment statistics
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Environment binding statistics
HIS HIS HIS Trnasformed to HISgtC HISgtC HISgtI
Filters
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Bound molecules form
Bonds details on atomic level
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Atomic bonds view
Atomic bonds statistics
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Atomic bonds statistics
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Detail forms header
Ligand binding statistics
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Ligand binding statistics
Filters
Distribution type
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Ligand binding statistics distribution by whole
environment
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Pattern binding statistics
Pattern H-x-H-E
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3D aligned views

• Superimposed by ligand
• Superimposed by environment
• Superimposed by pattern
• Superimposed by active site

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3D aligned views
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3D aligned views EBI-AstexViewertm