Electrostatics of proteins in dielectric solvent continua. II. Hamiltonian reaction field dynamics

Abstract

In Paper I of this work [S. Bauer, G. Mathias, and P. Tavan, J. Chem. Phys. 140, 104102 (2014)] we have presented a reaction field (RF) method, which accurately solves the Poisson equation for proteins embedded in dielectric solvent continua at a computational effort comparable to that of polarizable molecular mechanics (MM) force fields. Building upon these results, here we suggest a method for linearly scaling Hamiltonian RF/MM molecular dynamics (MD) simulations, which we call "Hamiltonian dielectric solvent" (HADES). First, we derive analytical expressions for the RF forces acting on the solute atoms. These forces properly account for all those conditions, which have to be self-consistently fulfilled by RF quantities introduced in Paper I. Next we provide details on the implementation, i.e., we show how our RF approach is combined with a fast multipole method and how the self-consistency iterations are accelerated by the use of the so-called direct inversion in the iterative subspace. Finally we demonstrate that the method and its implementation enable Hamiltonian, i.e., energy and momentum conserving HADES-MD, and compare in a sample application on Ac-Ala-NHMe the HADES-MD free energy landscape at 300K with that obtained in Paper I by scanning of configurations and with one obtained from an explicit solvent simulation.