Exploring A Multi-Scale Method for Molecular Simulations in Continuum Solvent Model: Explicit Simulation of Continuum Solvent As An Incompressible Fluid

TL;DR

This paper develops and validates a multi-scale molecular simulation framework coupling molecular mechanics with fluid dynamics to model continuum solvents, successfully reproducing solute-solvent interfaces and equilibria.

Contribution

It introduces a novel multi-scale simulation method integrating fluid dynamics with molecular mechanics in Amber, handling nonlinear van der Waals interactions analytically.

Findings

Successfully validated against analytical solutions.

Achieved equilibrium states with realistic solvent interfaces.

Good agreement with explicit water simulation boundaries.

Abstract

A multi-scale framework was recently proposed for more realistic molecular dynamics simulations in continuum solvent models by coupling a molecular mechanics treatment of solute with a fluid mechanics treatment of solvent, where we formulated the physical model and developed a numerical fluid dynamics integrator. In this study, we incorporated the fluid dynamics integrator with the Amber simulation engine to conduct atomistic simulations of biomolecules. At this stage of the development, only nonelectrostatic interactions, i.e., van del Waals and hydrophobic interactions are included in the multi-scale model. Nevertheless numerical challenges exist in accurately interpolating the highly nonlinear van del Waals term when solving the finite-difference fluid dynamics equations. We were able to bypass the challenge rigorously by merging the van del Waals potential and pressure together when solving the fluid dynamics equations and by considering its contribution in the free-boundary condition analytically. The multi-scale simulation engine was first validated by reproducing the solute-solvent interface of a single atom with analytical solution. Next, we performed the relaxation simulation of a restrained symmetrical monomer and observed a symmetrical solvent interface at equilibrium with detailed surface features resembling those found on the solvent excluded surface. Four typical small molecular complexes were then tested, both volume and force balancing analysis showing that these simple complexes can reach equilibrium within the simulation time window. Finally, we studied the quality of the multi-scale solute-solvent interfaces for the four tested dimer complexes and found they agree well with the boundaries as sampled in the explicit water simulations.