title: Vicinity analysis: a methodology for the identification of similar protein active sites.
abstract: Vicinity analysis (VA) is a new methodology developed to identify similarities between protein binding sites based on their three-dimensional structure and the chemical similarity of matching residues. The major objective is to enable searching of the Protein Data Bank (PDB) for similar sub-pockets, especially in proteins from different structural and biochemical series. Inspection of the ligands bound in these pockets should allow ligand functionality to be identified, thus suggesting novel monomers for use in library synthesis. VA has been developed initially using the ATP binding site in kinases, an important class of protein targets involved in cell signalling and growth regulation. This paper defines the VA procedure and describes matches to the phosphate binding sub-pocket of cyclin-dependent protein kinase 2 that were found by searching a small test database that has also been used to parameterise the methodology.
authors.affiliation: Centre for Molecular Design, Institute of Biomedical and Biomolecular Sciences, University of Portsmouth, King Henry Building, King Henry I St., Portsmouth PO12DY, UK.
authors.forename: A
authors.initials: A
authors.lastname: McGready
authors.forename: A
authors.initials: A
authors.lastname: Stevens
authors.forename: M
authors.initials: M
authors.lastname: Lipkin
authors.forename: B D
authors.initials: BD
authors.lastname: Hudson
authors.forename: D C
authors.initials: DC
authors.lastname: Whitley
authors.forename: M G
authors.initials: MG
authors.lastname: Ford
mesh_terms: D020134:Catalytic Domain; D002394:Catechol O-Methyltransferase / Q000737:chemistry; D019295:Computational Biology / Q000379:methods*; D017868:Cyclic AMP-Dependent Protein Kinases / Q000737:chemistry; D051357:Cyclin-Dependent Kinase 2 / Q000737:chemistry; D010710:Phosphates / Q000737:chemistry; D011506:Proteins / Q000737:chemistry*; D012372:ROC Curve; D019311:Staurosporine / Q000737:chemistry
chemical_list: D010710:Phosphates; D011506:Proteins; D002394:Catechol O-Methyltransferase; D017868:Cyclic AMP-Dependent Protein Kinases; D051357:Cyclin-Dependent Kinase 2; D019311:Staurosporine