New spherical‐cutoff methods for long‐range forces in macromolecular simulation

Abstract New atom‐ and group‐based spherical‐cutoff methods have been developed for the treatment of nonbonded interactions in molecular dynamics (MD) simulation. A new atom‐based method, force switching, leaves short‐range forces unaltered by adding a constant to the potential energy, switching forces smoothly to zero over a specified range. A simple improvement to group‐based cutoffs is presented: Switched group‐shifting shifts the group–group potential energy by a constant before being switched smoothly to zero. Also introduced are generalizations of atom‐based force shifting, which adds a constant to the Coulomb force between two charges. These new approaches are compared to existing methods by evaluating the energy of a model hydrogen‐bonding system consisting of two N ‐methyl acetamide molecules and by full MD simulation. Thirty‐five 150 ps simulations of carboxymyoglobin (MbCO) hydrated by 350 water molecules indicate that the new methods and atom‐based shifting are each able to approximate no‐cutoff results when a cutoff at or beyond 12 Å is used. However, atom‐based potential‐energy switching and truncation unacceptably contaminate group–group electrostatic interactions. Group‐based potential truncation should not be used in the presence of explicit water or other mobile electrostatic dipoles because energy is not a state function with this method, resulting in severe heating (about 4 K/ps in the simulations of hydrated MbCO). The distance‐dependent dielectric (ϵ ∝︁ r ) is found to alter the temperature dependence of protein dynamics, suppressing anharmonic motion at high temperatures. Force switching and force shifting are the best atom‐based spherical cutoffs, whereas switched group‐shifting is the preferred group‐based method. To achieve realistic simulations, increasing the cutoff distance from 7.5 to 12 Å or beyond is much more important than the differences among the three best cutoff methods. © 1994 by John Wiley & Sons, Inc. This article is a US Government work and, as such, is in the public domain in the United States of America.