ebi is an outstation of the european molecular biology laboratory. pdbechem the ligand database
TRANSCRIPT
EBI is an Outstation of the European Molecular Biology Laboratory.
PDBeChemThe Ligand Database
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, 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'- MONOPHOSPHATE 2'-DEOXY-L-RIBO-FURANOSYL CYTOSINE-5'-MONOPHOSPHATE
C9H14N3O7P
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
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
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
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
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
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.
PDBeChem: Search by Formula
Activate Formula editor
• 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
PDBeChem: Search by Fragment
Fragment search
• Web form
• Significant fragments
• Example : • More than 2 benzimidazoles
• No piperazine
• Anything else
PDBeChem: Search by Fragment
PDBeChem: Search by sub-structure
Activate JME molecule editor
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
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
EAA details
substructure of3-chloro-phenol
PDBeChem: Search by sub-structure
PDBeChem: Output formats for you!
Get the PDB entries that include EAA
Viewing & saving options
• 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