How Reproducible Are QM/MM Simulations? Lessons from Computational Studies of the Covalent Inhibition of the SARS-CoV-2 Main Protease by Carmofur
How Reproducible Are QM/MM Simulations? Lessons from Computational Studies of the Covalent Inhibition of the SARS-CoV-2 Main Protease by Carmofur
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DOI：
10.1021/acs.jctc.2c00286
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发表时间：
2022-07-07
影响因子：
5.5
通讯作者：
Krylov, Anna I.
中科院分区：
文献类型：
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作者：
Giudetti, Goran;Polyakov, Igor;Krylov, Anna I.
这项工作探讨了量子力学/分子力学（QM/MM）模拟的实际再现性所需的计算协议的细节报告的透明度。利用SARS-CoV-2必需酶的反应（主要蛋白酶）与共价抑制剂（卡莫氟）作为生物分子化学反应的测试案例，我们使用在两个软件包中实现的类似QM/MM模型进行QM/MM计算，以确定反应物、产物和过渡态/中间体的结构和能量，NWChem和Q-Chem。我们的主要基准测试目标是重现用这两个软件包计算的关键能量学。我们的研究结果表明，定量协议（在计算中使用的数值阈值）是难以实现的。我们表明，QM/ MM模拟的细节必须报告，以确保结果的再现性，并提供建议，制定实用的指导方针，报告生物模拟的结果。
This work explores the level of transparency in reporting the details of computational protocols that is required for practical reproducibility of quantum mechanics/molecular mechanics (QM/MM) simulations. Using the reaction of an essential SARS-CoV-2 enzyme (the main protease) with a covalent inhibitor (carmofur) as a test case of chemical reactions in biomolecules, we carried out QM/MM calculations to determine the structures and energies of the reactants, the product, and the transition state/intermediate using analogous QM/MM models implemented in two software packages, NWChem and Q-Chem. Our main benchmarking goal was to reproduce the key energetics computed with the two packages. Our results indicate that quantitative agreement (within the numerical thresholds used in calculations) is difficult to achieve. We show that rather minor details of QM/ MM simulations must be reported in order to ensure the reproducibility of the results and offer suggestions toward developing practical guidelines for reporting the results of biosimulations.