title: Functionality maps of binding sites: a multiple copy simultaneous search method.
abstract: A new method is proposed for determining energetically favorable positions and orientations for functional groups on the surface of proteins with known three-dimensional structure. From 1,000 to 5,000 copies of a functional group are randomly placed in the site and subjected to simultaneous energy minimization and/or quenched molecular dynamics. The resulting functionality maps of a protein receptor site, which can take account of its flexibility, can be used for the analysis of protein ligand interactions and rational drug design. Application of the method to the sialic acid binding site of the influenza coat protein, hemagglutinin, yields functional group minima that correspond with those of the ligand in a cocrystal structure.
authors.affiliation: Department of Chemistry, Harvard University, Cambridge, Massachusetts 02138.
authors.forename: A
authors.initials: A
authors.lastname: Miranker
authors.forename: M
authors.initials: M
authors.lastname: Karplus
mesh_terms: D001665:Binding Sites; D015195:Drug Design; D019267:Hemagglutinin Glycoproteins, Influenza Virus; D006389:Hemagglutinins, Viral / Q000737:chemistry*; D006860:Hydrogen Bonding; D008432:Mathematical Computing; D008958:Models, Molecular; D019158:N-Acetylneuraminic Acid; D011487:Protein Conformation; D012794:Sialic Acids / Q000737:chemistry*; D013499:Surface Properties
chemical_list: D019267:Hemagglutinin Glycoproteins, Influenza Virus; D006389:Hemagglutinins, Viral; D012794:Sialic Acids; D019158:N-Acetylneuraminic Acid