Functionally relevant protein motions: extracting basin-specific collective coordinates from molecular dynamics trajectories.
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.
Pan
Patricia Wang
PW
Department of Chemistry, Brock University, St. Catharines, Ontario L2S 3A1, Canada.
Dickson
Russell J
RJ
Gordon
Heather L
HL
Rothstein
Stuart M
SM
Tanaka
Shigenori
S
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
D001426:Bacterial Proteins; D012997:Solvents; C080951:Spo0F protein, Bacillus subtilis