Sampling of slow diffusive conformational transitions with accelerated molecular dynamics.
Slow diffusive conformational transitions play key functional roles in biomolecular systems. Our ability to sample these motions with molecular dynamics simulation in explicit solvent is limited by the slow diffusion of the solvent molecules around the biomolecules. Previously, we proposed an accelerated molecular dynamics method that has been shown to efficiently sample the torsional degrees of freedom of biomolecules beyond the millisecond timescale. However, in our previous approach, large-amplitude displacements of biomolecules are still slowed by the diffusion of the solvent. Here we present a unified approach of efficiently sampling both the torsional degrees of freedom and the diffusive motions concurrently. We show that this approach samples the configuration space more efficiently than normal molecular dynamics and that ensemble averages converge faster to the correct values.
Hamelberg
Donald
D
Howard Hughes Medical Institute, Center for Theoretical Biological Physics, Department of Chemistry and Biochemistry, University of California at San Diego, La Jolla, California 92093-0365, USA. dhamelbe@mccammon.ucsd.edu
de Oliveira
César Augusto F
CA
McCammon
J Andrew
JA
D002627:Chemistry, Physical / Q000379:methods*; D003198:Computer Simulation; D004058:Diffusion; D008958:Models, Molecular; D015233:Models, Statistical; D008962:Models, Theoretical; D008968:Molecular Conformation; D010100:Oxygen / Q000737:chemistry; D010455:Peptides / Q000737:chemistry; D012984:Software; D012997:Solvents / Q000737:chemistry; D013816:Thermodynamics; D013997:Time Factors; D014867:Water / Q000737:chemistry
D010455:Peptides; D012997:Solvents; D014867:Water; D010100:Oxygen