Fast switching alchemical simulations: a non equilibrium approach for drug discovery projects on parallel platforms

We present a novel all-atoms molecular dynamics approach for computing ligand-receptor binding free energies in drug discovery projects. The technique is a non equilibrium variant of the alchemical method[1] and effectively combines generalized ensemble (GE) and fast switching double annihilation (FSDAM) nonequilibrium (NE) technologies. The method is implemented in the ORAC program[2, 3]. The code was equipped with a hybrid Open Multi-Processing (OpenMP), Message Passing Interface (MPI) multilevel parallelism specifically tailored for non uniform memory access (NUMA) multi-core architectures. A demonstrative application of the FS-DAM approach on HPC platforms is presented.