GENERALIZED ALTERATION OF STRUCTURE AND PARAMETERS - A NEW METHOD FORFREE-ENERGY PERTURBATIONS IN SYSTEMS CONTAINING FLEXIBLE DEGREES OF FREEDOM

A modified derivation of the free energy perturbation (FEP) equation l eads to a more general interpretation of the procedures for generating the geometry of a perturbed molecule from the reference one in FEP si mulations of flexible systems. Using this form of the equation, it is possible to implement a wide variety of procedures which heretofore wo uld have been considered impossible. A new method, generalized alterat ion of structure and parameters (GASP), has been implemented in the BO SS program and has been found to be more efficient for perturbations o f harmonic degrees of freedom than the commonly adopted procedure. Add itionally, an extreme example for which the new procedure proves less satisfactory is presented, and a more efficient method which is also d erived from the new form of the FEP equation is devised and tested. It is concluded that the key to a convergent FEP method is efficient sam pling of low-energy configurations of the perturbed state; the new for m of the equation suggests ways of generating such configurations. (C) 1995 by John Wiley & Sons, Inc.