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质子化和互变异构在相对结合亲和力预测中的重要性：AMBER TI与薛定谔有限元微扰法的比较

The importance of protonation and tautomerization in relative binding affinity prediction: a comparison of AMBER TI and Schrödinger FEP.

作者信息

Hu Yuan, Sherborne Brad, Lee Tai-Sung, Case David A, York Darrin M, Guo Zhuyan

机构信息

Department of Chemistry Modeling & Informatics, Merck Research Laboratories, 2000 Galloping Hill Road, Kenilworth, NJ, 07033, USA.

Department of Chemistry and Chemical Biology, Center for Integrative Proteomics Research, BioMaPS Institute for Quantitative Biology, Rutgers University, Piscataway, NJ, 08854, USA.

出版信息

J Comput Aided Mol Des. 2016 Jul;30(7):533-9. doi: 10.1007/s10822-016-9920-5. Epub 2016 Aug 1.

DOI:10.1007/s10822-016-9920-5
PMID:27480697
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC6360336/
Abstract

In drug discovery, protonation states and tautomerization are easily overlooked. Through a Merck-Rutgers collaboration, this paper re-examined the initial settings and preparations for the Thermodynamic Integration (TI) calculation in AMBER Free-Energy Workflows, demonstrating the value of careful consideration of ligand protonation and tautomer state. Finally, promising results comparing AMBER TI and Schrödinger FEP+ are shown that should encourage others to explore the value of TI in routine Structure-based Drug Design.

摘要

在药物研发过程中，质子化状态和互变异构现象很容易被忽视。通过默克公司与罗格斯大学的合作，本文重新审视了AMBER自由能工作流程中热力学积分（TI）计算的初始设置和准备工作，证明了仔细考虑配体质子化和互变异构状态的价值。最后，展示了比较AMBER TI和薛定谔FEP+的有前景的结果，这应该会鼓励其他人去探索TI在基于结构的常规药物设计中的价值。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c536/6360336/baa6066c92c3/nihms-994588-f0014.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c536/6360336/9101f7c26706/nihms-994588-f0013.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c536/6360336/baa6066c92c3/nihms-994588-f0014.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c536/6360336/9101f7c26706/nihms-994588-f0013.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c536/6360336/baa6066c92c3/nihms-994588-f0014.jpg

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