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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

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PDBeChem: Search by Formula

PDBeChem: Search by Fragment

Fragment search

• Web form

• Significant fragments

• Example : • More than 2 benzimidazoles

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PDBeChem: Search by Fragment

PDBeChem: Search by sub-structure

Activate JME molecule editor

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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