1. EMBL-EBI Chemistry & the PDB MSDchem Primary Developer: Dimitris Dimitropoulos

2. EMBL-EBI The chemical database

3. EMBL-EBI MSDchem ligand dictionary  Complete, clean, up to date collection of all the chemical species and small molecules in the PDB  A ligand in MSDchem is a complete, distinct stereo isomer of a chemical compound  Atoms and element types  Bonds and bond orders  Stereo configuration of atoms and bonds in cases of stereo-isomers (R/S – E/Z)  Atom names and coordinates are not fundamental properties

4. EMBL-EBI Role in the MSD database  An integral component in the core of MSD database  Relational reference from entities where a molecule or atom name is used in the PDB (protein residues and atoms)  It is not possible for an ATOM line: HETATM 4342 C2 PLA 86 14.227 11.195 -8.256 1.00 67.95 C to be loaded if the “PLA” ligand is not defined or it does not include a “C2” atom.

5. EMBL-EBI Chemistry and PDB  Eliminate chemical inconsistencies from new PDB entries  Structure and derived properties of a ligand apply automatically to residues and bound molecules that reference it  The basic structure is carefully determined during curation, and a rich set of derived attributes is calculated for each ligand  Graph isomorphism is being applied to check the consistency of the PDB, taking stereo-configuration into account  Old legacy PDB entries are chemically “corrected” when loaded in the MSD database  In thousands of cases errors are identified and corrected, involving most of them times inconsistent naming or different stereo-configuration  Exchanged in cooperation with RCSB and the wwPDB

6. EMBL-EBI More than just the PDB codes All ligands are modelled as separate inter-related ligands and the appropriate one is referenced  No distinction is made in the PDB between ribo- and deoxyribonucleotides (all are identified with the same residue name i.e., A, C, G, T, U, I)  Modified nucleic acids are given as +A etc regardless of modification  No distinction between different topological variants (12 different variants can be found for HIS in PDB)

7. EMBL-EBI Derived information  External scientific software (CACTVS, VEGA, CORINA, ACD-labs, CCP4, OELIB) together with in house development has been used to derive:  Stereochemistry (R/S – E/Z) 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  Smiles and detailed gifs  Systematic IUPAC names

8. EMBL-EBI Derived information Fingerprints:  A bit string in hexadecimal form that indicates the presence or not of segments from predefined lists  Useful for fast search and classification  Different libraries of predefined lists can be set  Currently calculated for the CACTVS library (500 segments) MoleculeSegments BitStrin g 1 0 1 0 1 0 Fingerprint: 2A

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10. EMBL-EBI Search options  By ligand code  By ligand name or synonym  By formula or formula range  By non stereo substructure  By non stereo superstructure  By exact stereo or non stereo structure  By fingerprint similarity  By fragment expression

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12. Clear structureDelete atomChange atom type after drawing bonds JME editor allows generation of SMILE string to enter search mode Click when complete

13. EMBL-EBI 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

14. EAA details substructure of 3-chloro-phenol

15. Get the PDB entries that include EAA Get the bound molecule instances and site interaction details Viewing & saving options

16. EMBL-EBI KWT (1S,6BR,9AS,11R,11BR)-9A,11B-DIMETHYL-1-[(METHYLOXY)METHYL]- 3,6,9-TRIOXO-1,6,6B,7,8,9,9A,10,11,11B-DECAHYDRO-3H-FURO[4,3,2- DE]INDENO[4,5-H][2]BENZOPYRAN-11-YL ACETATE 55 31 0 COC[C@H]1OC(=O)c2coc3C(=O)C4=C([C@@H](C[C@@]5(C)[C@H]4 CCC5=O)OC(C)=O)[C@]1(C)c23 (1S,6bR,9aS,11R,11bR)-1-(methoxymethyl)-9a,11b-dimethyl-3,6,9- trioxo-1,6,6b,7,8,9,9a,10,11,11b-decahydro-3H-furo[4,3,2-de]indeno[4,5- h]isochromen-11-yl acetate PDB residue KWT

17. EMBL-EBI Formula-fragment expression search Formula expression Example: Search for ligands with more than 10 oxygens no nitrogens and sulphurs Fragment expression Example: Search for ligands with furan rings but not any saturated carbon rings (cyclobutane,cyclopropane,cyclohexane)