Classical Density Functional Theory for Implicit Solvent Simulations

Abstract

Molecular dynamics simulations can be sped up if implicit solvent algorithms can accurately capture the effects of water without simulating water explicitly. We will describe a classical density functional theory that we have developed to investigate interactions between proteins and solvents--including denaturants, osmolytes, and crowding agents in addition to water. We use this approach to reproduce transfer free energies reported elsewhere, and show that the cDFT model captures the desolvation barrier and the temperature dependence of the transfer free energy. Along the way we give a proof that the free energy of a bath of particles in a finite external potential is independent of the external potential in the isothermal-isobaric ensemble. We finally discuss the challenges remaining in implementing our implicit solvent model.