Transcript PPT
PDBeChem The Ligand Database EBI is an Outstation of the European Molecular Biology Laboratory. 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) What is a “Ligand” in PDB? • • Bound molecules (e.g. Sugars, lipids, inhibitors, biological coenzymes and cofactors), standard and modified amino acids and nucleic acids, atoms (metal, halogens, unknown atom) Identified by a unique 3 Letter code • atoms, element type, connectivity, bond orders, stereochemical configuration Source of Information -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 on a daily basis among the wwPDB partners Accommodates new entries and modifications from wwPDB partners Explicit connectivity and bond orders Representative co-ordinates (both model and ideal) http://www.wwpdb.org/ccd.html 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 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 PDBeChem refinement New entries better depositions clean-up Archive curation Curation better curation better load PDBe DB The PDBeChem database • Collection of all chemical species and small molecules in the PDB • • A ligand is a distinct stereo-isomer • • • • Complete, up to date Atoms and element types Bonds and bond orders Stereo configuration of atoms and bonds in cases of stereoisomers (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 Derived properties • • For Stereochemistry (R/S – E/Z) Cheminformatics software used systematically in PDBeChem • • CACTVS, CORINA, VEGA, ACD-labs In-house development DCF DCM C4' R C4' S C3' S C3' R C1' R C1' S THIOALANINE (ALT) • • Smiles and detailed gifs Systematic IUPAC names CC(N)C(O)=S - C[C@H](N)C(O)=S (2S)-2-aminopropanethioic O-acid 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 nonstereo structure PDBeChem By fingerprint similarity Some uses: By fragment expression • • • Search for drug or ligands. Understand chemistry of ligand. Download ‘ideal’ coordinates for own analysis (docking etc) and study. PDBeChem: Search by Formula Activate the editor PDBeChem: Searching by Chemical 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 PDBeChem: Search by Fragment Activate the Editor PDBeChem: Search by Fragment • Web form • Significant fragments • Example : • More than 2 benzimidazoles • No piperazine • Anything else PDBeChem: Search by sub-structure Activate the JME Editor PDBeChem: Search by sub-structure Delete atom Change atom type after drawing bonds JME editor allows generation of SMILE string to enter search mode Click when complete Results from using search by substructure Search criteria PDBeChem: Search by sub-structure Substructure of 3-chlorophenol Atoms and Bond Description for DCN PDBeChem: Output formats for you! Additional information about the ligand Chemsearch Results