The principle behind the ESMACS family of protocols is that many short simulations provide better sampling than single long simulations, facilitating the rapid and reproducible calculation of binding affinities using variations of MMPBSA. The ESMACS simulation and analysis workflow has been automated using the Binding Affinity Calculator (BAC) which we have recently enhanced using Radical Cybertools to create HTBAC . The goal of HTBAC is to provide a programmable interface to create computational pipelines built from selected software tools and services, and execute them on remote resources. It automates much of the complexity of running and marshaling the molecular dynamics simulations, as well as collecting and analyzing data.