Hybrid integral equation/simulation model for enhancing free energy computations

Abstract

Integral equation theory is used for extrapolating free energy data from molecular simulations of a reference state with respect to a modification of the interaction potential. The methodology is applied to the correction of artefacts arising from potential shifting and truncation. Corrective contributions for the hydration free energy with respect to the full potential are analysed for the case that both the solute–solvent as well as the solvent–solvent potentials are truncated and modified by a shifted-force term, reaching beyond the range of the dielectric continuum approximation and simple long-range correction expressions. The model systems argon in water and pure water are used as examples for apolar and polar solutes, revealing significant correction contributions even for the short-ranged dispersive interactions and the magnitude of solute–solvent and solvent–solvent components. In comparison with simulation-based extrapolation techniques the integral equation method is shown to be capable of quantitatively predicting truncation artefacts at negligible computational overhead.