Generalized ensembles serve to improve the convergence of free energy simulations

A novel method for the calcn. of the free energy difference between two states of a mol. system is presented.  The method, an extension of thermodn. integration, treats the coupling parameter λ as a variable in an extended Hamiltonian formulation and propagates it with the phys. coordinates.  In the resulting generalized ensemble, the crossing of barriers in the phys. space is enhanced.  The free energy difference is detd. by integrating the reversible work required to move λ from zero (corresponding to the initial state) to one (corresponding to the final state).  Examples are presented to illustrate the method.