Computing accurate potentials of mean force in electrolyte solutions with the generalized gradient-augmented harmonic Fourier beads method.

ABSTRACT

We establish the accuracy of the novel generalized gradient-augmented harmonic Fourier beads (ggaHFB) method in computing free-energy profiles or potentials of mean force (PMFs) through comparison with two independent conventional techniques. In particular, we employ umbrella sampling with one dimensional weighted histogram analysis method (WHAM) and free molecular dynamics simulation of radial distribution functions to compute the PMF for the Na(+)-Cl(-) ion-pair separation to 16 A in 1.0M NaCl solution in water. The corresponding ggaHFB free-energy profile in six dimensional Cartesian space is in excellent agreement with the conventional benchmarks. We then explore changes in the PMF in response to lowering the NaCl concentration to physiological 0.3 and 0.1M, and dilute 0.0M concentrations. Finally, to expand the scope of the ggaHFB method, we formally develop the free-energy gradient approximation in arbitrary nonlinear coordinates. This formal development underscores the importance of the logarithmic Jacobian correction to reconstruct true PMFs from umbrella sampling simulations with either WHAM or ggaHFB techniques when nonlinear coordinate restraints are used with Cartesian propagators. The ability to employ nonlinear coordinates and high accuracy of the computed free-energy profiles further advocate the use of the ggaHFB method in studies of rare events in complex systems.