We have developed a new simulation algorithm for free-energy calculations.
The method is a multidimensional extension of the replica-exchange method.
While pairs of replicas with different temperatures are exchanged during th
e simulation in the original replica-exchange method, pairs of replicas wit
h different temperatures and/or different parameters of the potential energ
y are exchanged in the new algorithm. This greatly enhances the sampling of
the conformational space and allows accurate calculations of free energy i
n a wide temperature range from a single simulation run, using the weighted
histogram analysis method. (C) 2000 American Institute of Physics. [S0021-
9606(00)50739-9].