title: Multiscale characterization of protein conformational ensembles.
abstract: We propose a multiscale exploration method to characterize the conformational space populated by a protein at equilibrium. The method efficiently obtains a large set of equilibrium conformations in two stages: first exploring the entire space at a coarse-grained level of detail, then narrowing a refined exploration to selected low-energy regions. The coarse-grained exploration periodically adds all-atom detail to selected conformations to ensure that the search leads to regions which maintain low energies in all-atom detail. The second stage reconstructs selected low-energy coarse-grained conformations in all-atom detail. A low-dimensional energy landscape associated with all-atom conformations allows focusing the exploration to energy minima and their conformational ensembles. The lowest energy ensembles are enriched with additional all-atom conformations through further multiscale exploration. The lowest energy ensembles obtained from the application of the method to three different proteins correctly capture the known functional states of the considered systems.
authors.affiliation: Department of Computer Science, Rice University, Houston, Texas 77005, USA.
authors.forename: Amarda
authors.initials: A
authors.lastname: Shehu
authors.forename: Lydia E
authors.initials: LE
authors.lastname: Kavraki
authors.forename: Cecilia
authors.initials: C
authors.lastname: Clementi
mesh_terms: D000263:Adenylate Kinase / Q000737:chemistry; D000818:Animals; D064026:Calbindins; D002147:Calmodulin / Q000737:chemistry; D003198:Computer Simulation; D006801:Humans; D008958:Models, Molecular; D011487:Protein Conformation; D011506:Proteins / Q000737:chemistry*; D064030:S100 Calcium Binding Protein G / Q000737:chemistry
chemical_list: D064026:Calbindins; D002147:Calmodulin; D011506:Proteins; D064030:S100 Calcium Binding Protein G; D000263:Adenylate Kinase