From docking to dynamics: Unveiling the potential non-peptide and non-covalent inhibitors of Mpro from natural products

被引：0
|
作者：
Zhang, Xin [1 ,2 ]
Zhao, Shulin [1 ]
Su, Xi [3 ]
Xu, Lifeng [1 ]
机构：
[1] The Quzhou Affiliated Hospital of Wenzhou Medical University, Quzhou People's Hospital, Quzhou, China
[2] Yangtze Delta Region Institute (Quzhou), University of Electronic Science and Technology of China, Quzhou, China
[3] Foshan Women and Children Hospital, Foshan, China
来源：
Computers in Biology and Medicine | 2024年 / 181卷
关键词：
Motivation: This study aims to investigate non-covalent and non-peptide inhibitors of Mpro; a crucial protein target; by employing a comprehensive approach that integrates molecular docking; molecular dynamics simulations; and top-hits activity predictions. The focus is on elucidating the non-covalent and non-peptide binding modes of potential inhibitors with Mpro. Methods: We employed a semi-flexible molecular docking methodology; binding score and ADME screening; which are based on structure; to screen compounds from CMNPD and HERB in silico. These methodologies allowed us to find potential candidates depending on their binding values and interactions with the binding site of main protease. To further evaluate the stability of these interactions; we conducted molecular dynamics simulations and calculated binding energies. Ultimately; a top-hits activity prediction method was employed to prioritize compounds based on their predicted inhibitory potential. Results: Through a combination of binding energy calculations and activity predictions; we identified six potential inhibitor molecules exhibiting promising activity against Mpro. These compounds demonstrated favorable binding interactions and stability profiles; making them attractive candidates for further experimental validation and drug development efforts targeting Mpro. © 2024;
D O I：
10.1016/j.compbiomed.2024.108963
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