Transcript PDBeChem_23Jul2009

PDBeChem
The Ligand Database
Gaurav Sahni, Ph.D.
EBI is an Outstation of the European Molecular Biology Laboratory.
Why PDBeChem?
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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?
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Bound molecules, standard and modified amino acids
and nucleic acids, atoms
Absolute stereochemistry, atoms, bonds, bond orders
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Unique 3-letter code
C9H14N3O7P
DFC
C4' R
C3' S
C1' R
2'-DEOXY-L-RIBO-FURANOSYL CYTOSINE-5'-MONOPHOSPHATE
DCM
C4' S
C3' R
C1' S
2'- DEOXYCYTIDINE- 5'- MONOPHOSPHATE
The wwPDB Ligand Dictionary
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Chemical Component Dictionary
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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
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” ?
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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
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Collection of all chemical species and small molecules in
the PDB
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A ligand is a distinct stereo-isomer
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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
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But there is a consistent set of identifiers
• Atoms, bond order, and stereochemistry
• Derived properties
Derived properties
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For Stereochemistry (R/S – E/Z)
Cheminformatics software used systematically in
PDBeChem
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CACTVS, CORINA, VEGA, ACD-labs
In-house development
DCF
DCM
C4' R
C4' S
C3' S
C3' R
C1' R
C1' S
THIOALANINE (ALT)
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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
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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
By fingerprint similarity
By fragment expression
Some uses:
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Search for drug or ligands.
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Understand chemistry of ligand.
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Download ‘ideal’ coordinates for
own analysis (docking etc) and
study.
PDBeChem: Search by Formula
Activate Formula
editor
PDBeChem: Search by 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
Fragment search
PDBeChem: Search by Fragment
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• Significant
fragments
• Example :
• More than 2
benzimidazoles
• No piperazine
• Anything else
PDBeChem: Search by sub-structure
Activate JME
molecule editor
PDBeChem: Search by sub-structure
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 of
3-chloro-phenol
PDBeChem: Output formats for you!
Viewing & saving
options
Get the PDB
entries that include
EAA
Summary
• 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
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)