title: A novel method for the modelling of peptide ligands to their receptors.
abstract: A knowledge-based approach to the modelling of enzyme-peptide inhibitor complexes is described. Given the structure of an enzyme, and knowledge of its binding site, the method seeks to predict the binding geometry of a peptide ligand. This novel method involves using examples of side-chain packing derived from proteins of known three-dimensional structure to define possible packing arrangements of a peptide inhibitor group to its binding site. A suite of programs, GEMINI, was written and used to predict the packing of pairs of amino acid groups from three inhibitors complexed to their enzymes for which the X-ray structures were available. These included the Phe group of the inhibitor H142 bound to endothiapepsin, the Leu group of CLT complexed to thermolysin and the C-terminus of Gly-L-Tyr bound to carboxypeptidase A. A detailed comparison of the modelled and observed inhibitor coordinates was made. This approach may be extended to modelling other types of protein interactions.
authors.affiliation: Department of Crystallography, Birkbeck College, University of London, UK.
authors.forename: J
authors.initials: J
authors.lastname: Singh
authors.forename: J
authors.initials: J
authors.lastname: Saldanha
authors.forename: J M
authors.initials: JM
authors.lastname: Thornton
mesh_terms: D016282:Aspartic Acid Endopeptidases / Q000037:antagonists & inhibitors / Q000737:chemistry*; D001665:Binding Sites; D002268:Carboxypeptidases / Q000037:antagonists & inhibitors / Q000737:chemistry*; D043422:Carboxypeptidases A; D003198:Computer Simulation; D016208:Databases, Factual; D004791:Enzyme Inhibitors / Q000737:chemistry*; D008024:Ligands; D008958:Models, Molecular; D011487:Protein Conformation; D013820:Thermolysin / Q000037:antagonists & inhibitors / Q000737:chemistry*
chemical_list: D004791:Enzyme Inhibitors; D008024:Ligands; D002268:Carboxypeptidases; D043422:Carboxypeptidases A; D016282:Aspartic Acid Endopeptidases; C042466:Endothia aspartic proteinase; D013820:Thermolysin