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Adel Golovin MSDsite

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". MSDsite. Introduction.

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Adel Golovin MSDsite

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  1. 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"

  2. MSDsite

  3. 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.

  4. 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. Ligand environment

  5. 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

  6. 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

  7. Covalent Bonds • Coordinate bonds • Hydrogen bonds • Planes • Non-bonding • Electrostatics • Di-Sulphide bonds • Geometry (distance, angles..) Structure DB N Site DB ASP PHE O S PHE VAL Environment Ligand environment analysis

  8. 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 Possible site searches

  9. Structure Protein Ligand Metal site geometry Environment exact/sub set Filter by PDB header: equal/like Define target: equal/like Sequence motif Search criteria Search options

  10. Statistics search Ligand binding Atomic bonds Interactive Charts Environment binding Sequence pattern binding

  11. Search method Search front form Statistics search Result list Detail views

  12. MSDsite interface Query editor Filters

  13. Query generation HIS|SER:S/H>C2.0 HIS.NE2:S/S>C2.0 HIS.[N]/T>C2.0 Drawing Complex queries secondary structure Distance cut-offs Bond type Side/main chain

  14. 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. Search service aims

  15. Example Pattern is defined as : HIS-any-HIS-GLU

  16. Hit List Help

  17. Hit List Visualization tools AstexViewer@MSD-EBI: Default PDB viewer: chemical/x-pdb. RasMol script viewer: application/x-rasmol.

  18. Searched site visualization AstexViewer[tm] Groups menu

  19. Hit List Link to Details Goto Site details Bound molecules form Sequence from Atomic bonds

  20. Detail forms header Links to the other views of the same PDB entry Ligand binding statistics Switch on/off undefined bonds

  21. Sequence form search for PDB entries with the same hetero ID and similar environment Show site

  22. Bound molecules form Ligands that match a search creteria Environment statistics

  23. Environment binding statistics HIS HIS HIS Trnasformed to HIS>C HIS>C HIS>I Filters

  24. Bound molecules form Bonds details on atomic level

  25. Atomic bonds view Atomic bonds statistics

  26. Atomic bonds statistics

  27. Detail forms header Ligand binding statistics

  28. Ligand binding statistics Filters Distribution type

  29. Ligand binding statistics – distribution by whole environment

  30. Pattern binding statistics Pattern: H-x-H-E

  31. Superimposed by ligand Superimposed by environment Superimposed by pattern Superimposed by active site 3D aligned views

  32. 3D aligned views

  33. 3D aligned views – EBI-AstexViewer[tm]

  34. 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

  35. Future sites 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.

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