Our ESMACS protocols are flexible, allowing for the analysis to be tailored to the target system. Previous targets we have studied include small molecule inhibitors of HIV proteins , kinases and larger more flexible ligands such as peptides which bind to MHC . In all these studies correlation coefficients of better than 0.7 were obtained. MMPBSA is most commonly used to assess binding affinities from a single trajectory of a protein bound to its target ligand but in this work we explore the influence of protein and ligand flexibility using independent trajectories.