Exploring epigenetic drugs as potential inhibitors of SARS-CoV-2 main protease: a docking and MD simulation study

Uzuner, Uğur; Akkus, Ebru; Kocak, Abdulkadır; Uzuner, Selcen Çelik

doi:10.1080/07391102.2023.2236714

Cited by 1 publication

(1 citation statement)

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“…[ 41 ]) with default and empirical parameters of 0.127 and −5.11, respectively. As reported by Akkus et al [ 41 ], these parameters were optimized SARS-CoV-2 M pro and have been successfully used in other studies [ 42 , 47 , 48 , 55 , 56 ].…”

Section: Methodsmentioning

confidence: 99%

Benchmarking ANI potentials as a rescoring function and screening FDA drugs for SARS-CoV-2 Mpro

Zengin,

Koca,

Tayfuroglu

et al. 2024

J Comput Aided Mol Des

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Here, we introduce the use of ANI-ML potentials as a rescoring function in the host–guest interaction in molecular docking. Our results show that the “docking power” of ANI potentials can compete with the current scoring functions at the same level of computational cost. Benchmarking studies on CASF-2016 dataset showed that ANI is ranked in the top 5 scoring functions among the other 34 tested. In particular, the ANI predicted interaction energies when used in conjunction with GOLD-PLP scoring function can boost the top ranked solution to be the closest to the x-ray structure. Rapid and accurate calculation of interaction energies between ligand and protein also enables screening of millions of drug candidates/docking poses. Using a unique protocol in which docking by GOLD-PLP, rescoring by ANI-ML potentials and extensive MD simulations along with end state free energy methods are combined, we have screened FDA approved drugs against the SARS-CoV-2 main protease (Mpro). The top six drug molecules suggested by the consensus of these free energy methods have already been in clinical trials or proposed as potential drug molecules in previous theoretical and experimental studies, approving the validity and the power of accuracy in our screening method.

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