Fast Switching Alchemical Transformations in Molecular Dynamics Simulations

We present an efficient and rigorous implementation of the fast switching alchemical transformation for systems where electrostatic interactions are treated using the smooth particle mesh Ewald method. Free energies are computed using bidirectional nonequilibrium alchemical trajectories by applying the Crooks fluctuation theorem and the Bennett acceptance ratio to the collection of the final alchemical works. The technique is used for the evaluation of the 1-octanol/water partition coefficients for some selected organic molecules. Fast switching alchemical tranformations appear to be competitive, both in accuracy and in efficiency, with respect to the traditional methods based on independent equilibrium simulations of intermediate states.