Application of the multiensemble sampling to the hydration free energy.

We demonstrate the feasibility of using multiensemble sampling method (MESM) to determine the free energy difference between two far states for which the configurational distributions do not overlap at all. The MESM is a recently developed non-Boltzmann sampling technique. The free energy of charging a sodium ion in water is accurately calculated in a single simulation, introducing nine intermediate ionic states. This is due to the ability of the method to explore the relevant parts of configuration space equally for every state, and this ability comes from the universality of weighting function W and the simplicity in adjusting its parameters. Detailed procedures of adjusting the parameters are presented. The comparison with a free energy perturbation method (FEPM) shows that the MESM is more reliable and efficient. (C) 2001 John Wiley & Sons, Inc. J Comput Chem 22: 1004-1009, 2001.