ABSTRACT
Electrostatic forces are crucial interatomic forces in molecular systems. Accurate representation of the electrostatic interactions remains a grand challenge in molecular modeling and simulations (Ren et al. 2011a). Fundamentally, the electrostatic interaction can be described by Coulomb’s law, as employed in most classical force elds, including AMBER (Cornell et al. 1995), CHARMM
(MacKerell et al. 1998), GROMOS (Valdes et al. 2008), MM3 (Lii and Allinger 1989a,b), and OPLS (Jorgensen et al. 1996). In these force elds, the polarization eect is implicitly included in the parameters, by increasing or decreasing the magnitude of the partial charges in an average fashion. Because many force elds target water environment, the partial charges are typically overestimated compared to the gas-phase values obtained from high-level quantum mechanical calculations. For decades, the classic force elds have gone through extensive renements, validations, and tests (Ponder and Case 2003, Rezac et al. 2008). is generation of force elds is now widely used in the studies of molecular structures, dynamics, and interactions. One challenge faced by such force elds, however, is that the electrostatics is unable to respond to environmental changes including dielectric constant, pH value, or nature of solvent.
