title: Characterization of protein conformational states by normal-mode frequencies.
abstract: Conformational change in polymers including proteins is central to many molecular processes. Defining conformational states, however, remains a difficult and increasingly common problem, with many existing methods based on arbitrary or potentially unrepresentative measures. Furthermore, the expanding length of molecular dynamics simulations and direct observation of transitions between different energy basins suggest that this issue will only become evermore important. Methods commonly used to characterize conformational states include principal component analysis, root-mean-square deviation-based clustering, and geometric measurements such as hinge angles and distances. Here we present a method where the eigenvector frequencies derived from a Gaussian network model (Bahar, I.; Atilgan, A. R.; Erman, B. Folding Des. 1997, 2, 173-181) of a trajectory of structures from a molecular dynamics simulation are used to describe the state of the protein at each time point. We apply the method to three proteins that share the same fold as the type II periplasmic binding proteins: The lysine-arginine-ornithine-binding protein, the glutamine-binding protein, and the ligand-binding domain from the NR1 N-methyl-D-aspartate receptor. We find that the method can distinguish different states in good agreement with a variety of previous analyses and additionally provides information on the dynamic properties of that system at a given time point.
authors: Department of Biochemistry, University of Oxford, South Parks Road, Oxford, OX1 3QU, U.K.
authors: Benjamin A
authors: BA
authors: Hall
authors: Samantha L
authors: SL
authors: Kaye
authors: Andy
authors: A
authors: Pang
authors: Rafael
authors: R
authors: Perera
authors: Philip C
authors: PC
authors: Biggin
mesh_terms: D001426:Bacterial Proteins / Q000737:chemistry; D002352:Carrier Proteins / Q000737:chemistry; D003198:Computer Simulation; D008024:Ligands; D008958:Models, Molecular; D033902:Periplasmic Binding Proteins / Q000737:chemistry; D011487:Protein Conformation; D017510:Protein Folding; D011506:Proteins / Q000737:chemistry*; D016194:Receptors, N-Methyl-D-Aspartate / Q000737:chemistry
chemical_list: D001426:Bacterial Proteins; D002352:Carrier Proteins; D008024:Ligands; C409466:NR1 NMDA receptor; D033902:Periplasmic Binding Proteins; D011506:Proteins; D016194:Receptors, N-Methyl-D-Aspartate; C037853:glutamine transport proteins; C033849:lysyl-arginyl-ornithine-binding protein, bacteria