FREE-ENERGY OF SOLVATION OF A SMALL LENNARD-JONES PARTICLE

In molecular dynamics (MD) and Monte Carlo (MC) free energy calculations, the choices of the thermodynamic paths from state a to state b affect the accuracy of the result and the efficiency of the programs. Most of the problems occur at the initial stages of growing in a new particle into a solvent. Based on statistical mechanical perturbation theory, an accurate and efficient direct calculation of inserting a small Lennard-Jones particle into solvent is derived. This eliminates the need for calculation of the initial stages of growing in a new particle by MD or MC simulation. Examples are given to show the utility of direct calculation. The recommended procedure is to use direct calculation for a small Lennard-Jones particle and then use MD or MC simulations to calculate the Delta G of changing the small Lennard-Jones particle into the target molecule. (C) 1994 by John Wiley and Sons, Inc.