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

IF 4.3 3区 材料科学 Q1 ENGINEERING, ELECTRICAL & ELECTRONIC
Irem N. Zengin, M. Serdar Koca, Omer Tayfuroglu, Muslum Yildiz, Abdulkadir Kocak
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引用次数: 0

Abstract

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.

将 ANI 电位作为重构函数的基准,并筛选用于 SARS-CoV-2 Mpro 的 FDA 药物。
在此,我们介绍在分子对接中使用 ANI-ML 电位作为主客体相互作用的重新评分函数。我们的研究结果表明,在计算成本相同的情况下,ANI 电位的 "对接能力 "可以与当前的评分函数相媲美。在 CASF-2016 数据集上进行的基准研究表明,在其他 34 种测试的评分函数中,ANI 位列前 5。特别是,ANI预测的相互作用能与GOLD-PLP评分函数结合使用时,能使排名第一的解决方案与X射线结构最接近。快速准确地计算配体与蛋白质之间的相互作用能还能筛选数百万个候选药物/对接方案。我们采用了一种独特的方案,将 GOLD-PLP 的对接、ANI-ML 电位的重构、大量 MD 模拟以及终态自由能方法结合在一起,针对 SARS-CoV-2 主要蛋白酶(Mpro)筛选出了经 FDA 批准的药物。这些自由能方法一致推荐的前六种药物分子已经进入临床试验阶段,或在以前的理论和实验研究中被推荐为潜在的药物分子,这证明了我们筛选方法的有效性和准确性。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
CiteScore
7.20
自引率
4.30%
发文量
567
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