title: Conformational change path between closed and open forms of C2 domain of coagulation factor V on a two-dimensional free-energy surface.
abstract: We test a hypothesis that the closed form of the C2 domain of coagulation factor V is more stable than the open form in an aqueous environment using a two-dimensional free-energy calculation with a simple dielectric solvent model. Our result shows that while the free-energy difference between two forms is small, favoring the closed form, a two-dimensional free-energy surface (FES) reveals that a transition state (1.53 kcal/mol) exists between the two conformations. By mapping the one-dimensional order parameter DeltaQ onto the two-dimensional FES, we search the conformational change path with the highest Boltzmann weighting factor between the closed and open form of the factor V C2 domain. The predicted transition path from the closed to open form is not that of simple side chain movements, but instead concerted movements of several loops. We also present a one-dimensional free-energy profile using a collective order parameter, which in a coarse manner locates the energy barriers found on the two-dimensional FES.
authors.affiliation: Department of Chemistry, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599-3290, USA.
authors.forename: Sangwook
authors.initials: S
authors.lastname: Wu
authors.forename: Chang Jun
authors.initials: CJ
authors.lastname: Lee
authors.forename: Lee G
authors.initials: LG
authors.lastname: Pedersen
mesh_terms: D000465:Algorithms; D005165:Factor V / Q000737:chemistry*; D008958:Models, Molecular; D009010:Monte Carlo Method; D011487:Protein Conformation; D017510:Protein Folding; D055550:Protein Stability; D013816:Thermodynamics; D014867:Water / Q000737:chemistry*
chemical_list: D014867:Water; D005165:Factor V