Generation of OPLS-like charges from molecular electrostatic potential using restraints

A new method for generating atom-centered charges for use in condensed phas e computer simulations is presented, which is based on a restrained electro static potential (RESP) procedure. Charges are calculated from a least-squa res fit to the quantum mechanical electrostatic potential with a restraint applied to reduce their magnitude. The restraint developed here offers adva ntages over that used in RESP. The magnitude of the restraint is optimized to yield charges as close to the equivalent OPLS values as possible while s till reproducing the molecule's electrostatic potential. A cross-validation analysis is used to show that the restraint is insensitive to the selectio n of OPLS molecules from which it is derived. Thus, with this method, OPLS- like charges may be produced from the electrostatic potential for atom type s not in the OPLS force field. In addition, the restraint is shown to reduc e the conformational dependence of the charges. (C) 1999 John Wiley & Sons, Inc.