Message passing interface and multithreading hybrid for parallel molecular docking of large databases on petascale high performance computing machines

A mixed parallel scheme that combines message passing interface (MPI) and multithreading was implemented in the AutoDock Vina molecular docking program. The resulting program, named VinaLC, was tested on the petascale high performance computing (HPC) machines at Lawrence Livermore National Laboratory. To exploit the typical cluster-type supercomputers, thousands of docking calculations were dispatched by the master process to run simultaneously on thousands of slave processes, where each docking calculation takes one slave process on one node, and within the node each docking calculation runs via multithreading on multiple CPU cores and shared memory. Input and output of the program and the data handling within the program were carefully designed to deal with large databases and ultimately achieve HPC on a large number of CPU cores. Parallel performance analysis of the VinaLC program shows that the code scales up to more than 15K CPUs with a very low overhead cost of 3.94%. One million flexible compound docking calculations took only 1.4 h to finish on about 15K CPUs. The docking accuracy of VinaLC has been validated against the DUD data set by the re-docking of X-ray ligands and an enrichment study, 64.4% of the top scoring poses have RMSD values under 2.0 Å. The program has been demonstrated to have good enrichment performance on 70% of the targets in the DUD data set. An analysis of the enrichment factors calculated at various percentages of the screening database indicates VinaLC has very good early recovery of actives.