title: Geometry-based sampling of conformational transitions in proteins.
abstract: The fast and accurate prediction of protein flexibility is one of the major challenges in protein science. Enzyme activity, signal transduction, and ligand binding are dynamic processes involving essential conformational changes ranging from small side chain fluctuations to reorientations of entire domains. In the present work, we describe a reimplementation of the CONCOORD approach, termed tCONCOORD, which allows a computationally efficient sampling of conformational transitions of a protein based on geometrical considerations. Moreover, it allows for the extraction of the essential degrees of freedom, which, in general, are the biologically relevant ones. The method rests on a reliable estimate of the stability of interactions observed in a starting structure, in particular those interactions that change during a conformational transition. Applications to adenylate kinase, calmodulin, aldose reductase, T4-lysozyme, staphylococcal nuclease, and ubiquitin show that experimentally known conformational transitions are faithfully predicted.
authors.affiliation: Computational Biomolecular Dynamics Group, Max-Planck-Institute for Biophysical Chemistry, Am Fassberg 11, 37077 Göttingen, Germany.
authors.forename: Daniel
authors.initials: D
authors.lastname: Seeliger
authors.forename: Jürgen
authors.initials: J
authors.lastname: Haas
authors.forename: Bert L
authors.initials: BL
authors.lastname: de Groot
mesh_terms: D000263:Adenylate Kinase / Q000737:chemistry; D000449:Aldehyde Reductase / Q000737:chemistry; D001665:Binding Sites; D002147:Calmodulin / Q000737:chemistry; D019295:Computational Biology / Q000379:methods*; D003198:Computer Simulation; D030562:Databases, Protein; D008024:Ligands; D008836:Micrococcal Nuclease / Q000737:chemistry; D008958:Models, Molecular; D009113:Muramidase / Q000737:chemistry; D011487:Protein Conformation; D011506:Proteins / Q000737:chemistry / Q000378:metabolism; D025801:Ubiquitin / Q000737:chemistry
chemical_list: D002147:Calmodulin; D008024:Ligands; D011506:Proteins; D025801:Ubiquitin; D000449:Aldehyde Reductase; D000263:Adenylate Kinase; D008836:Micrococcal Nuclease; D009113:Muramidase