Application of the linearized MD approach for computing equilibrium solvation free energies of charged and dipolar solutes in polar solvents

The linearized MD technique is developed in order to. treat systematically free energies of simple charged and dipolar solutes in water. The solvent electrostatic response field in the solute region is modeled by averaging instantaneous fields found in a MD computation for solvent configurations confined within a cavity that conforms to the real shape of the solute particle. At this stage, all electrostatic interactions are explicitly treated inside the cavity. The solvent in the external region (outside the cavity) is modeled in terms of a standard continuum theory. For nonspherical cavities, the present approach is more accurate than the field computation employed at the preceding MD stage, where spherically truncated Coulomb potentials are modified by the reaction field corrections. We considered two different linearization schemes based on a computation of either the average response field or of its fluctuations. Only the first algorithm proved to be successful. For a series of single-charged monatomic cations and anions, it provides free energies that deviate by few percent from those found in full MD computations. The results are stable relative to a separation of the whole space occupied by the solvent into explicit solvent region (inside the cavity) and the continuum region (outside the cavity). The two-site dipolar dumbbell system was also studied in the range of intersite separation D within 2 Angstrom < D < 10 Angstrom. At the stage of the field computation, three different types of its solvation shell were considered: spherical and bispherical cavities and periodic solvent environment monitored in terms of Ewald method. Free solvation energies are the same (within 1 kcal/mol) for all three models. A smooth dependence of the mean field potential is observed as a function of separation D but its asymptotic value differs by 4 kcal/mol from the free energy computed for the isolated ion pair. The results generally agree with those obtained in the literature in terms of full MD simulations.