1. Estimation of Potentials of Mean Force from Nonequilibrium Pulling Simulations Using Both Minh-Adib Estimator and Weighted Histogram Analysis Method
- Author
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Ngo, Van A., Kim, Ilsoo, Allen, Toby W., and Noskov, Sergei Y.
- 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.
- Published
- 2016
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