Fluctuating charge force fields: recent developments and applications from small molecules to macromolecular biological systems

The past decade has seen intense development of what are anticipated to be the next generation of classical force fields to be used in computational statistical mechanical approaches to studying a broad class of physical and biological systems. Among the several approaches being actively pursued currently is the fluctuating charge (or equivalently charge equilibration or electronegativity equalization) method. Within this formalism, dynamical electronic degrees of freedom are introduced and propagated in time in order to allow an electrostatic response to the local chemical environment. In this article, we present a review of our recent development and application efforts of a polarizable biomolecular force field based on the fluctuating charge formalism and founded on the CHARMM non-polarizable force field. We will discuss aspects of the parameterization, as well as recent applications to a spectrum of chemical and biological systems such as small-molecule liquid–vapor interfaces, solvated proteins/peptides, and physiological membrane systems. We will conclude with brief comments on aspects that require continued effort in terms of future development of such novel potentials.