Multiscale Modeling of Solvation

Abstract

Statistical-mechanical, reference interaction site model (RISM ) molecular theory of solvation is promising as an essential part of multiscale methodology for chemical and biomolecular nanosystems in solution. Beginning with a force field of site interaction potentials between solution species, it uses a diagrammatic analysis of the solvation free energy to construct integral equations for 3-D spatial correlation functions of molecular interaction sites in the statistical–mechanical ensemble. With the solvation structure so obtained at the level of molecular simulation, 3D-RISM-KH further yields the solvation thermodynamics at once as a simple integral of the correlation functions which is obtained by performing thermodynamic integration analytically. The latter allows analytical differentiation of the free energy functional and thus self-consistent coupling in various multiscale approaches. 3D-RISM-KH has been coupled with the KS-DFT and CASSCF quantum chemistry methods in a self-consistent field description of electronic structure, geometry optimization, nanochemistry, and photochemistry in solution. The multiple time step molecular dynamics of biomolecules steered by effective solvation forces obtained from the 3D-RISM-KH theory, accelerated by the generalized solvation force extrapolation, and stabilized by the optimized isokinetic Nose–Hoover chain (OIN) thermostat, enables gigantic outer time steps up to tens picoseconds to accurately calculate equilibrium properties.