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PDBeChem: The Ligand Database for Protein Chemistry

PDBeChem is a reference dictionary for the chemical definition of 3-letter coded single residues in the PDB. It holds the single residue definitions for the PDB and represents it for all other databases at the EBI. Search for ligand structures easily using PDBeChem's search system.

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PDBeChem: The Ligand Database for Protein Chemistry

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  1. PDBeChem The Ligand Database Gaurav Sahni, Ph.D.

  2. Why PDBeChem? • Link between protein and chemistry • Reference dictionary for the chemical definition of 3 letter coded single residues in the PDB (wwPDB CCD) • Holds the single residue definitions for the PDB and represents it for all other databases at the EBI (PDBeChem database) • How else will you find ligand structures !!!!! (PDBeChem search system)

  3. C9H14N3O7P DCM C4' S C3' R C1' S DFC C4' R C3' S C1' R 2'-DEOXY-L-RIBO-FURANOSYL CYTOSINE-5'-MONOPHOSPHATE 2'- DEOXYCYTIDINE- 5'- MONOPHOSPHATE What is a “Ligand” in PDB? • Bound molecules, standard and modified amino acids and nucleic acids, atoms • Absolute stereochemistry, atoms, bonds, bond orders • Unique 3-letter code

  4. The wwPDB Ligand Dictionary • Chemical Component Dictionary • Reference dictionary, one record for each, different 3-letter code • As mmCif file, available through ftp • Exchanged and synchronised every day between wwPDB partners • Accommodates new entries and modifications from wwPDB partners • Explicit connectivity and bond orders • Representative co-ordinates data_ATP # _chem_comp.id ATP _chem_comp.name 'ADENOSINE-5'-TRIPHOSPHATE' _chem_comp.type non-polymer _chem_comp.pdbx_type HETAIN _chem_comp.formula 'C10 H16 N5 O13 P3' _chem_comp.mon_nstd_flag n http://www.wwpdb.org/ccd.html

  5. PDBeChem Archive clean-up refinement curation better load PDBe DB New entries Curation better depositions better curation Why have a “Dictionary” ? • Eliminate chemical inconsistencies from new entries through better curation • Legacy PDB entries are chemically “corrected” when loaded in PDBe • Energy types used by refinement libraries improve new depositions • Improvements are exchanged between wwPDB partners

  6. The PDBeChem database • Collection of all chemical species and small molecules in the PDB • Complete, up to date • A ligand is a distinct stereo-isomer • Atoms and element types • Bonds and bond orders • Stereo configuration of atoms and bonds in cases of stereo-isomers (R/S – E/Z) • Names and co-ordinates not fundamental • But there is a consistent set of identifiers • Atoms, bond order, and stereochemistry • Derived properties

  7. DCF C4' R C3' S C1' R DCM C4' S C3' R C1' S THIOALANINE (ALT) CC(N)C(O)=S - C[C@H](N)C(O)=S (2S)-2-aminopropanethioic O-acid Derived properties • For Stereochemistry (R/S – E/Z) • Cheminformatics software used systematically in PDBeChem • CACTVS, CORINA, VEGA, ACD-labs • In-house development • Smiles and detailed gifs • Systematic IUPAC names

  8. Some uses: • Search for drug or ligands. • Understand chemistry of ligand. • Download ‘ideal’ coordinates for own analysis (docking etc) and study. Search options • By ligand code • By ligand name or synonym • By formula or formula range • By non-stereo smile • By stereo smile • By exact stereo or non- stereo structure • By fingerprint similarity • By fragment expression

  9. PDBeChem: Search by Formula Activate Formula editor

  10. PDBeChem: Search by Formula • Expression can be built with web form • Example : O1-4 N3-100 F0 • 1 to 4 oxygens • More than 3 nitrogens • No Fluorine • Anything else

  11. PDBeChem: Search by Fragment Fragment search

  12. PDBeChem: Search by Fragment • Web form • Significant fragments • Example : • More than 2 benzimidazoles • No piperazine • Anything else

  13. Activate JME molecule editor PDBeChem: Search by sub-structure

  14. Clear structure Delete atom Change atom type after drawing bonds JME editor allows generation of SMILE string to enter search mode Click when complete PDBeChem: Search by sub-structure

  15. Search for ligand structures containing 3-chloro-phenol Results Get PDB entries and bound molecule instances containing 3-chloro-phenol Click to get Details for EAA PDBeChem: Search by sub-structure

  16. EAA details substructure of3-chloro-phenol PDBeChem: Search by sub-structure

  17. PDBeChem: Output formats for you! Viewing & saving options Get the PDB entries that include EAA

  18. Summary • The wwPDB ligand dictionary provides the chemistry of the PDB • The original PDBeChem database has been merged in the remediation project • The state of the dictionary has improved • The PDBeChem web application provides searching of the dictionary • Name • Formula • Substructure • Fragments - similarity

  19. Why PDBeChem? • Link between protein and chemistry • Reference dictionary for the chemical definition of 3 letter coded single residues in the PDB (wwPDB CCD) • Holds the single residue definitions for the PDB and represents it for all other databases at the EBI (PDBeChem database) • How else will you find ligand structures !!!!! (PDBeChem search system)

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