  We study the conformational equilibria of two peptides using a novel
statistical mechanics approach designed for calculating free energy differences
between highly dis-similar conformational states. Our results elucidate the
contrasting roles of entropy in implicitly solvated leucine dipeptide and
decaglycine. The method extends earlier work by Voter, and overcomes the
notorious "overlap" problem in free energy computations by constructing a
mathematically equivalent calculation with high conformational similarity. The
approach requires only equilibrium simulations of the two states of interest,
without the need for sampling transition states. We discuss extensions of the
approach to binding affinity estimation and explicitly solvated systems, as
well as possible optimizations.
