Large-scale binding affinity calculations on commodity compute clouds

Abstract

In recent years, it has become possible to calculate binding affinities of compounds bound to proteins via rapid, accurate, precise and reproducible free energy calculations. This is imperative in drug discovery as well as personalized medicine. This approach is based on molecular dynamics (MD) simulations and draws on sequence and structural information of the protein and compound concerned. Free energies are determined by ensemble averages of many MD replicas, each of which requires hundreds of cores and/or GPU accelerators, which are now available on commodity cloud computing platforms; there are also requirements for initial model building and subsequent data analysis stages. To automate the process, we have developed a workflow known as the binding affinity calculator. In this paper, we focus on the software infrastructure and interfaces that we have developed to automate the overall workflow and execute it on commodity cloud platforms, in order to reliably predict their binding affinities on time scales relevant to the domains of application, and illustrate its application to two free energy methods.