title: Estimation of Potentials of Mean Force from Nonequilibrium Pulling Simulations Using Both Minh-Adib Estimator and Weighted Histogram Analysis Method.
abstract: Nonequilibrium pulling simulations have been a useful approach for investigating a variety of physical and biological problems. The major target in the simulations is to reconstruct reliable potentials of mean force (PMFs) or unperturbed free-energy profiles for quantitatively addressing both equilibrium mechanistic properties and contributions from nonequilibrium processes. While several current nonequilibrium methods were shown to be accurate in computing free-energy profiles in systems with relatively simple dynamics, they have proved to be unsuitable in more complicated systems. To extend the applicability of nonequilibrium sampling, we demonstrate a novel method that combines Minh-Adib's bidirectional estimator with nonlinear WHAM equations to reconstruct and assess PMFs from relatively fast pulling trajectories. We test the method in a one-dimensional model system and in a system of an antibiotic gramicidin-A (gA) channel, which is considered a significant challenge for nonequilibrium sampling. We identify key parameters for efficiently performing pulling simulations to improve and ensure the convergence and accuracy of estimated PMFs. We show that a few pulling trajectories of a relatively fast pulling speed v = 10 Å/ns can return a fair estimate of the PMF of a single potassium ion in gA.
authors.affiliation: Centre for Molecular Simulation, Department of Biological Sciences, University of Calgary , Alberta, AB T2N 1N4, Canada.
authors.forename: Van A
authors.initials: VA
authors.lastname: Ngo
authors.affiliation: Department of Chemistry, University of Southern California , Los Angeles, California United States.
authors.forename: Ilsoo
authors.initials: I
authors.lastname: Kim
authors.affiliation: School of Applied Science and Health Innovations Research Institute, RMIT University , Melbourne, 3000, Australia and.|Department of Chemistry, University of California , Davis California 95616, United States.
authors.forename: Toby W
authors.initials: TW
authors.lastname: Allen
authors.affiliation: Centre for Molecular Simulation, Department of Biological Sciences, University of Calgary , Alberta, AB T2N 1N4, Canada.
authors.forename: Sergei Y
authors.initials: SY
authors.lastname: Noskov
mesh_terms: D000900:Anti-Bacterial Agents / Q000737:chemistry*; D006096:Gramicidin / Q000737:chemistry*; D008051:Lipid Bilayers / Q000737:chemistry; D013816:Thermodynamics
chemical_list: D000900:Anti-Bacterial Agents; D008051:Lipid Bilayers; D006096:Gramicidin