PDBeChem

1. PDBeChem The Ligand Database

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. 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

4. 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) 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. PDBeChem • 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 the editor

10. 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

11. PDBeChem: Search by Fragment Activate the Editor

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

13. PDBeChem: Search by sub-structure Activate the JME Editor

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

15. Results from using search by substructure Search criteria

16. PDBeChem: Search by sub-structure Substructure of 3-chlorophenol

17. Atoms and Bond Description for DCN

18. PDBeChem: Output formats for you!

19. Additional information about the ligand

20. Chemsearch

21. Results