embl-ebi adel golovin msdsite the project is funded by the european commission as the temblor,...
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EMBL-EBI
Adel Golovin
MSDsite
The project is funded by the European Commission as the TEMBLOR, contract-no. QLRI-CT-2001-00015 under the RTD programme "Quality of Life and Management of Living Resources"
EMBL-EBI
MSDsite
EMBL-EBI
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.
Introduction
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The 3D / 1D position that defines the protein functiondisparate amino acids on the 1D sequenceA localized volume in 3D
Where chemistry/binding happens.
Ligand environment
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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-nucleic-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
MSD site database
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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/thornton-srv/databases/CSA/ Merops active sites
http://merops.sanger.ac.uk/
Site definitions
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Covalent Bonds Coordinate bonds Hydrogen bonds Planes Non-bonding Electrostatics Di-Sulphide bonds Geometry (distance,
angles..)
PHE
PHE
O
N
S
ASP
VAL
Ligand environment
analysis Site DB
StructureDB
Environment
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Define search by ligand Define search by sequence motif (pattern) Define search by metal site geometry Define search by environment
has same environmenthas similar environment
Possible site searches
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Structure
ProteinLigand
Define target:
equal/like
Filter by PDB header:
equal/like
Environmentexact/sub set
Searchcriteria
Sequencemotif
Metal site
geometry
Search options
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Statistics search
Interactive Charts
Ligand binding
Environment binding
Atomic bonds
Sequence pattern binding
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Search method
Search front form
Statistics search
Result list
Detail views
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MSDsite interface
Filters
Queryeditor
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HIS|SER:S/H>C2.0 HIS.NE2:S/S>C2.0 HIS.[N]/T>C2.0
Drawing Complex queries
secondary structureDistance cut-offs
Bond typeSide/main chain
Query generation
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Search service aims
Form a site search criteriaProvide a hit list
Visualize the found sitesXML 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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AstexViewer@MSD-EBI :
Default PDB viewer: chemical/x-pdb.
RasMol script viewer: application/x-rasmol.
Hit List Visualization tools
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Searched site visualization
AstexViewer[tm]Groups menu
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Goto Site details
Hit List Link to Details
Bound molecules form
Sequence from
Atomic bonds
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Detail forms header
Ligand binding statistics
Links to the other views of the same
PDB entrySwitch on/off
undefined bonds
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Show site
Sequence form
search for PDB entries with the same hetero ID and similar environment
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Bound molecules form
Ligands that match a search
creteria
Environment statistics
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Environment binding statistics
FiltersHIS HIS HISTrnasformed to HIS>C HIS>C HIS>I
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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
Distribution type
Filters
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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-AstexViewer[tm]
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EMBL-EBI
DB of active sites has been generated Application server has been developed The DB can be searched
Based on properties of the ligand environment Based on properties of the ligand Based on properties of structure and sequence of the parent
protein
Summary
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Data generated by data mining of common packing of chemical groups is being added. (Proteins S.F.G, 49:510-528, T.J.Oldfield). This information contains about 2000 sites, 1/3 with ligands.
Future sites