title: Functionally relevant protein motions: extracting basin-specific collective coordinates from molecular dynamics trajectories.
abstract: Functionally relevant motion of proteins has been associated with a number of atoms moving in a concerted fashion along so-called "collective coordinates." We present an approach to extract collective coordinates from conformations obtained from molecular dynamics simulations. The power of this technique for differentiating local structural fluctuations between classes of conformers obtained by clustering is illustrated by analyzing nanosecond-long trajectories for the response regulator protein Spo0F of Bacillus subtilis, generated both in vacuo and using an implicit-solvent representation. Conformational clustering is performed using automated histogram filtering of the inter-C(alpha) distances. Orthogonal (varimax) rotation of the vectors obtained by principal component analysis of these interresidue distances for the members of individual clusters is key to the interpretation of collective coordinates dominating each conformational class. The rotated loadings plots isolate significant variation in interresidue distances, and these are associated with entire mobile secondary structure elements. From this we infer concerted motions of these structural elements. For the Spo0F simulations employing an implicit-solvent representation, collective coordinates obtained in this fashion are consistent with the location of the protein's known active sites and experimentally determined mobile regions.
authors.affiliation: Department of Chemistry, Brock University, St. Catharines, Ontario L2S 3A1, Canada.
authors.forename: Patricia Wang
authors.initials: PW
authors.lastname: Pan
authors.forename: Russell J
authors.initials: RJ
authors.lastname: Dickson
authors.forename: Heather L
authors.initials: HL
authors.lastname: Gordon
authors.forename: Stuart M
authors.initials: SM
authors.lastname: Rothstein
authors.forename: Shigenori
authors.initials: S
authors.lastname: Tanaka
mesh_terms: D000595:Amino Acid Sequence; D001426:Bacterial Proteins / Q000737:chemistry*; D003198:Computer Simulation; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009038:Motion; D017434:Protein Structure, Tertiary; D012997:Solvents
chemical_list: D001426:Bacterial Proteins; D012997:Solvents; C080951:Spo0F protein, Bacillus subtilis