Non-Gaussian distributions of absolute free energies in ensemble molecular dynamics simulations

Significantly more ‘outliers’ can be produced from a non-Gaussian distribution than one would anticipate were the statistics to conform to a normal distribution. Using ensemble simulations consisting of 25 replicas, we have previously identified a considerable percentage of ligand-protein systems which present non-Gaussian distributions in calculated binding free energies. Here we report on the statistics of much larger ensemble and find that the free energy distributions are definitively non-Gaussian for these systems.