Supercomputer-Based Ensemble Docking Drug Discovery Pipeline with Application to Covid-19

Journal of Chemical Information and Modeling, Год журнала: 2020, Номер 60(12), С. 5832 - 5852

Опубликована: Дек. 16, 2020

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

Язык: Английский

Variants in ACE2; potential influences on virus infection and COVID-19 severity

Infection Genetics and Evolution, Год журнала: 2021, Номер 90, С. 104773 - 104773

Опубликована: Фев. 17, 2021

Язык: Английский

Supercomputer-Based Ensemble Docking Drug Discovery Pipeline with Application to Covid-19

Опубликована: Июль 29, 2020

We present a supercomputer-driven pipeline for

Язык: Английский