title: A comparison of structural and dynamic properties of different simulation methods applied to SH3.
abstract: The dynamic and static properties of molecular dynamics simulations using various methods for treating solvent were compared. The SH3 protein domain was chosen as a test case because of its small size and high surface-to-volume ratio. The simulations were analyzed in structural terms by examining crystal packing, distribution of polar residues, and conservation of secondary structure. In addition, the "essential dynamics" method was applied to compare each of the molecular dynamics trajectories with a full solvent simulation. This method proved to be a powerful tool for the comparison of large concerted atomic motions in SH3. It identified methods of simulation that yielded significantly different dynamic properties compared to the full solvent simulation. Simulating SH3 using the stochastic dynamics algorithm with a vacuum (reduced charge) force field produced properties close to those of the full solvent simulation. The application of a recently described solvation term did not improve the dynamic properties. The large concerted atomic motions in the full solvent simulation as revealed by the essential dynamics method were analyzed for possible biological implications. Two loops, which have been shown to be involved in ligand binding, were seen to move in concert to open and close the ligand-binding site.
authors.affiliation: Department of Biochemistry and Molecular Biology, University of Leeds, England. aalten@bmbpcu01.leeds.ac.uk
authors.forename: D M
authors.initials: DM
authors.lastname: van Aalten
authors.forename: A
authors.initials: A
authors.lastname: Amadei
authors.forename: R
authors.initials: R
authors.lastname: Bywater
authors.forename: J B
authors.initials: JB
authors.lastname: Findlay
authors.forename: H J
authors.initials: HJ
authors.lastname: Berendsen
authors.forename: C
authors.initials: C
authors.lastname: Sander
authors.forename: P F
authors.initials: PF
authors.lastname: Stouten
mesh_terms: D000465:Algorithms; D001665:Binding Sites; D055592:Biophysical Phenomena; D001703:Biophysics; D003198:Computer Simulation; D003460:Crystallization; D008024:Ligands; D008956:Models, Chemical; D008958:Models, Molecular; D015394:Molecular Structure; D017433:Protein Structure, Secondary; D012997:Solvents; D013269:Stochastic Processes; D013816:Thermodynamics; D018909:src Homology Domains / Q000502:physiology*
chemical_list: D008024:Ligands; D012997:Solvents