1. EBI is an Outstation of the European Molecular Biology Laboratory. 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, standard and modified amino acids and nucleic acids, atoms Absolute stereochemistry, atoms, bonds, bond orders Unique 3-letter code DFC C4' R C3' S C1' R DCM C4' S C3' R C1' S 2'- DEOXYCYTIDINE- 5'- MONOPHOSPHATE2'-DEOXY-L-RIBO-FURANOSYL CYTOSINE-5'-MONOPHOSPHATE C 9 H 14 N 3 O 7 P

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. 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 Curation PDBeChem PDBe DB Archive New entries refinement curation clean-up better depositions better curation better load

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. 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 THIOALANINE (ALT) CC(N)C(O)=S - C[C@H](N)C(O)=S (2S)-2-aminopropanethioic O-acid DCF C4' R C3' S C1' R DCM C4' S C3' R C1' S

8. 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 Some uses: Search for drug or ligands. Understand chemistry of ligand. Download ‘ideal’ coordinates for own analysis (docking etc) and study.

9. PDBeChem: Search by Formula Activate Formula editor

10. 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 Formula

11. PDBeChem: Search by Fragment Fragment search

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

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

14. Clear structureDelete atomChange 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 Click to get Details for EAA Get PDB entries and bound molecule instances containing 3-chloro-phenol PDBeChem: Search by sub-structure

16. EAA details substructure of 3-chloro-phenol PDBeChem: Search by sub-structure

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

18. 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 Summary

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)