Application of Poisson—Boltzmann solvation forces to macromolecular simulations

Abstract

One of the most difficult problems encountered in the dynamical simulation of large macromolecular systems is how to deal adequately with the huge number of atomic interactions involved. For aqueous-phase simulations the computational burden associated with solvent water molecules can easily outstrip that associated with the macromolecule, even though the behavior of the solvent itself may not be of much interest. Not surprisingly therefore, considerable interest has been focused on the use of methods in which explicit solvent water molecules are replaced by an implicit dielectric continuum representation; an excellent review of such methods was given by Sharp [1] in the previous volume of this series. Perhaps the most generally accepted continuum-based approach centers on the use of the Poisson—Boltzmann (PB) equation of classical electrostatics [2], a method which owes its success to the fact that many solvation-related phenomena (with the notable exception of the hydrophobic effect) appear to be essentially electrostatic in nature. Until very recently, use of the PB approach has largely been restricted to calculations involving static representations of molecular structure, but the recent development of methods to obtain solvation forces from the PB equation [3] means that it can now, in principle, also be used in dynamics simulations. Applications of the former type have been comprehensively reviewed in the literature [2] and are not discussed further in this article; instead, we restrict our attention to the potential use of PB electrostatics in dynamical simulations of macromolecules.