title: Predicting large-scale conformational changes in proteins using energy-weighted normal modes.
abstract: We report the development of a method to improve the sampling of protein conformational space in molecular simulations. It is shown that a principal component analysis of energy-weighted normal modes in Cartesian coordinates can be used to extract vectors suitable for describing the dynamics of protein substructures. The method can operate with either atomistic or user-defined coarse-grained models of protein structure. An implicit reverse coarse-graining allows the dynamics of all-atoms to be recovered when a coarse-grained model is used. For an external test set of four proteins, it is shown that the new method is more successful than normal mode analysis in describing the large-scale conformational changes observed on ligand binding. The method has potential applications in protein-ligand and protein-protein docking and in biasing molecular dynamics simulations.
authors: Department of Chemistry, Aarhus University, Aarhus C, Denmark.
authors: David S
authors: DS
authors: Palmer
authors: Frank
authors: F
authors: Jensen
mesh_terms: D056004:Molecular Dynamics Simulation; D011487:Protein Conformation; D011506:Proteins / Q000737:chemistry*
chemical_list: D011506:Proteins