title: A hierarchical method for generating low-energy conformers of a protein-ligand complex.
abstract: A novel dynamical protocol for finding the low-energy conformations of a protein-ligand complex is described. The energy functions examined consist of an empirical force field with four different dielectric screening models; the generalized Born/surface area model also is examined. Application of the method to three complexes of known crystal structure provides insights into the energy functions used for selecting low-energy docked conformations and into the structure of the binding-energy surface. Evidence is presented that the local energy minima of a ligand in a binding site are arranged in a hierarchical fashion. This observation motivates the construction of a hierarchical docking algorithm that substantially enriches the population of ligand conformations close to the crystal conformation. The algorithm is also adapted to permit docking into a flexible binding site and preliminary tests of this method are presented.
authors.affiliation: Center for Advanced Research in Biotechnology, Rockville, Maryland 20850, USA.
authors.forename: J A
authors.initials: JA
authors.lastname: Given
authors.forename: M K
authors.initials: MK
authors.lastname: Gilson
mesh_terms: D000465:Algorithms; D001665:Binding Sites; D003461:Crystallography; D008024:Ligands; D015233:Models, Statistical; D008968:Molecular Conformation; D015394:Molecular Structure; D011485:Protein Binding; D011487:Protein Conformation; D017433:Protein Structure, Secondary; D011506:Proteins / Q000737:chemistry
chemical_list: D008024:Ligands; D011506:Proteins