| 引用本文： |
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甘雨满,刘永宏,刘锴.结合自由能微扰积分法及其在药物研发中的应用[J].广西科学,2020,27(5):493-502. [点击复制]
- GAN Yuman,LIU Yonghong,LIU Kai.Application and Research Progress of Binding Free Energy Perturbation Calculation in Drug Discovery[J].Guangxi Sciences,2020,27(5):493-502. [点击复制]
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| 摘要: |
| 以分子动力学为基础的泊松-玻尔兹曼（或广义玻恩）分子表面法（Molecular Mechanics/Poisson-Boltzmann（or Generalized Born）Surface Area，MM/PB（GB）SA）在药物研发过程中取得巨大成功。与MM/PB（GB）SA计算相比，结合自由能微扰积分法通过构建严谨的热力学循环，可对结合自由能进行精确计算，但因为其计算量巨大，所以在实际中应用相对较少。近年来，随着高性能计算机的发展和动力学模拟技术的革新，基于结合自由能微扰积分法的结合自由能计算逐渐成为研究热点。本文简要介绍了以分子动力学为基础的结合自由能微扰积分法的计算过程及其相关联的限制势增强动力学采样技术，并通过具体的实例展现结合自由能微扰积分法在药物研发中的应用前景。 |
| 关键词: 分子动力学模拟 自由能计算 微扰积分法 热力学循环 药物设计 |
| DOI：10.13656/j.cnki.gxkx.20201214.007 |
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| 基金项目:国家自然科学地区基金项目（31960019），广西高校引进海外高层次人才“百人计划”项目（桂教师范[2019]71号），广西自然科学青年基金项目（2019GXNSFBA185023），广西中医药大学新进博士科研启动项目（2018BS038，2018BS044），广西高校中青年教师科研基础能力提升项目（2019KY0326），广西中医药大学海洋药物研究院团队科研专项（2018ZD005），广西八桂学者专项（05019055）和广西中医药大学岐黄工程高层次人才团队培育项目（2018006）资助。 |
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| Application and Research Progress of Binding Free Energy Perturbation Calculation in Drug Discovery |
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GAN Yuman1, LIU Yonghong1,2, LIU Kai1
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| (1.Institute of Marine Drugs, Guangxi University of Chinese Medicine, Nanning, Guangxi, 530200, China;2.CAS Key Laboratory of Tropical Marine Bio-resources and Ecology, South China Sea Institute of Oceanology, Chinese Academy of Sciences, Guangzhou, Guangdong, 510301, China) |
| Abstract: |
| Molecular Mechanics/Poisson Boltzmann (or Generalized Born) Surface Area (MM/PB(GB)SA) based on molecular dynamics is has achieved great success in the process of drug development.Compared with MM/PB(GB)SA calculation,the combined free energy perturbation (FEP) integral method can accurately calculate the combined free energy by constructing a rigorous thermodynamic cycle,but because of its huge amount of calculation,it is relatively less used in practice.In recent years,with the development of high-performance computers and the innovation of dynamic simulation technology,the calculation of combined free energy based on the perturbation integral method of combined free energy has gradually become a research hotspot.This article briefly introduces the calculation process of the combined free energy perturbation integral method based on molecular dynamics and its associated confined potential enhanced dynamic sampling technology,and demonstrates the application prospects of the combined free energy perturbation integration method in drug development through specific examples. |
| Key words: molecular dynamics free energy calculation perturbation theory thermodynamic cycle drug design |
