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

Abstract

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.

GABA A receptor target of tetramethylenedisulfotetramine

“…Type A compounds include EBOB and many insecticides with large substituents or extended structures, and the type B set includes TETS, TBPS, TBPO, and other small compact molecules, some of very high i.p. toxicity to mice (LD 50 36 μg/kg for TBPO) (25) (SI Appendix, section S8), although much less toxic to injected houseflies (LD 50 90 mg/kg for TETS) (4). The target site mapping studies above suggest a molecular distinction between the binding of type A compounds and Type B cage convulsants (32).…”

“…The GABA A R α 1 β 2 γ 2 homology model was built with a GluCl template (PDB ID code 3RHW) (48) using previously published protocols (36,37). Small molecules were parameterized with the PRODRG server (49) and docked into the pore using VinaLC (50). The proteinligand system was embedded in a lipid bilayer and solvated.…”

VinaMPI: Facilitating multiple receptor high-throughput virtual docking on high-performance computers

“…A recent paper [17] uses a similar parent-child distribution scheme as with Autodock4.lga.MPI but with the Autodock Vina docking engine. Using this approach, a nearly linear speed-up is achieved on 15,000 cores.…”

Adverse Drug Reaction Prediction Using Scores Produced by Large-Scale Drug-Protein Target Docking on High-Performance Computing Machines

“…The docking accuracy of VinaLC has been validated against the DUD (Directory of Useful Decoys) database [34] by the re-docking of X-ray ligands and an enrichment study. The statistical results presented in their study [33] show VinaLC is one of the better performing docking codes on the DUD set of decoys/ligands, having a mean receiver operator characteristic area-under the curve (ROC AUC) of 0.64 (95 th CI: 0.60-0.68). VinaLC identified 64.4% of the top scoring poses with an RMSD under the 2.0 Å cutoff, while that for the best poses is 70.0%.…”

“…Zhang et al [33] implemented a mixed parallel scheme using Message Passing Interface (MPI) and multithreading in a parallel molecular docking program, called VinaLC, by modifying the existing AutoDock Vina molecular docking program. One million flexible docking calculations took about 1.4 hours to finish on ∼15 K CPUs.…”