Toward the correction of effective electrostatic forces in explicit-solvent molecular dynamics simulations: restraints on solvent-generated electrostatic potential and solvent polarization

Despite considerable advances in computing power, atomistic simulations under nonperiodic boundary conditions, with Coulombic electrostatic interactions and in systems large enough to reduce finite-size associated errors in thermodynamic quantities to within the thermal energy, are still not affordable. As a result, periodic boundary conditions, systems of microscopic size and effective electrostatic interaction functions are frequently resorted to. Ensuing artifacts in thermodynamic quantities are nowadays routinely corrected a posteriori, but the underlying configurational sampling still descends from spurious forces. The present study addresses this problem through the introduction of on-the-fly corrections to the physical forces during an atomistic molecular dynamics simulation. Two different approaches are suggested, where the force corrections are derived from special potential energy terms. In the first approach, the solvent-generated electrostatic potential sampled at a given atom site is restrained to a target value involving corrections for electrostatic artifacts. In the second approach, the long-range regime of the solvent polarization around a given atom site is restrained to the Born polarization, i.e., the solvent polarization corresponding to the ideal situation of a macroscopic system under nonperiodic boundary conditions and governed by Coulombic electrostatic interactions. The restraints are applied to the explicit-water simulation of a hydrated sodium ion, and the effect of the restraints on the structural and energetic properties of the solvent is illustrated. Furthermore, by means of the calculation of the charging free energy of a hydrated sodium ion, it is shown how the electrostatic potential restraint translates into the on-the-fly consideration of the corresponding free-energy correction terms. It is discussed how the restraints can be generalized to situations involving several solute particles. Although the present study considers a very simple system only, it is an important step toward the on-the-fly elimination of finite-size and approximate-electrostatic artifacts during atomistic molecular dynamics simulations. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s00214-014-1600-8) contains supplementary material, which is available to authorized users.