We present a supercomputer-driven pipeline for in silico drug discovery using enhanced sampling molecular dynamics (MD) and ensemble docking. Ensemble docking makes use of MD results by docking compound databases into representative protein binding-site conformations, thus taking into account the dynamic properties of the binding sites. We also describe preliminary results obtained for 24 systems involving eight proteins of the proteome of SARS-CoV-2. The MD involves temperature replica exchange enhanced sampling, making use of massively parallel supercomputing to quickly sample the configurational space of protein drug targets. Using the Summit supercomputer at the Oak Ridge National Laboratory, more than 1 ms of enhanced sampling MD can be generated per day. We have ensemble docked repurposing databases to 10 configurations of each of the 24 SARS-CoV-2 systems using AutoDock Vina. Comparison to experiment demonstrates remarkably high hit rates for the top scoring tranches of compounds identified by our ensemble approach. We also demonstrate that, using Autodock-GPU on Summit, it is possible to perform exhaustive docking of one billion compounds in under 24 h. Finally, we discuss preliminary results and planned improvements to the pipeline, including the use of quantum mechanical (QM), machine learning, and artificial intelligence (AI) methods to cluster MD trajectories and rescore docking poses.

A hybrid method is proposed to study atomic diffusion behavior in Cu-Al explosive welding process. The method combines molecular dynamics simulation and classical diffusion theory. Cu-Al explosive welding and scanning electron microscope experiments are done to verify the method. Using the method, we find that the atomic diffusion mostly takes place in the unloading stage of the welding process. The diffusion coefficients are collision velocity-dependent, with higher velocities generating larger coefficients. When there is no transverse velocity, the diffusion coefficient is directly proportional to the longitudinal velocity. With the longitudinal velocity fixed, the diffusion coefficient is proportional to the square of the transverse velocity. The thickness of the diffusion layer is calculated from the simulation result, and it is in good agreement with the experiment result. V