The MM/PBSA and MM/GBSA methods to estimate ligand-binding affinities.
The MM/PBSA and MM/GBSA methods to estimate ligand-binding affinities.
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DOI：
10.1517/17460441.2015.1032936
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发表时间：
2015-05
影响因子：
6.3
通讯作者：
Ryde U
中科院分区：
文献类型：
--
作者：
Genheden S;Ryde U
分子力学能结合泊松-玻尔兹曼或广义玻恩和表面积连续溶剂化（MM/PBSA和MM/GBSA）方法是估计小配体与生物大分子结合自由能的常用方法。它们通常基于受体-配体复合物的分子动力学模拟，因此在准确性和计算工作量方面介于经验评分和严格的炼金术摄动方法之间。它们已应用于大量系统，取得了不同程度的成功。涵盖的领域：作者回顾了MM/PBSA和MM/GBSA方法计算配体结合亲和力的使用，重点是校准，测试和验证，以及尝试改进方法，而不是具体应用。专家意见：MM/PBSA和MM/GBSA是有吸引力的方法，因为它们的模块化性质，它们不需要在训练集上进行计算。它们已被成功地用于再现和合理化实验结果，并改进虚拟筛选和对接的结果。然而，它们包含了一些粗糙和可疑的近似，例如，缺乏构象熵和关于结合点水分子数量和自由能的信息。此外，该方法有许多变体，其性能随被测系统的不同而有很大差异。同样，大多数试图用更精确的方法来改进方法的尝试，例如，量子力学计算，极化力场或改进溶剂化，都使结果恶化。
Introduction: The molecular mechanics energies combined with the Poisson–Boltzmann or generalized Born and surface area continuum solvation (MM/PBSA and MM/GBSA) methods are popular approaches to estimate the free energy of the binding of small ligands to biological macromolecules. They are typically based on molecular dynamics simulations of the receptor–ligand complex and are therefore intermediate in both accuracy and computational effort between empirical scoring and strict alchemical perturbation methods. They have been applied to a large number of systems with varying success. Areas covered: The authors review the use of MM/PBSA and MM/GBSA methods to calculate ligand-binding affinities, with an emphasis on calibration, testing and validation, as well as attempts to improve the methods, rather than on specific applications. Expert opinion: MM/PBSA and MM/GBSA are attractive approaches owing to their modular nature and that they do not require calculations on a training set. They have been used successfully to reproduce and rationalize experimental findings and to improve the results of virtual screening and docking. However, they contain several crude and questionable approximations, for example, the lack of conformational entropy and information about the number and free energy of water molecules in the binding site. Moreover, there are many variants of the method and their performance varies strongly with the tested system. Likewise, most attempts to ameliorate the methods with more accurate approaches, for example, quantum-mechanical calculations, polarizable force fields or improved solvation have deteriorated the results.
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影响因子：
2.2
作者：
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通讯作者：
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影响因子：
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影响因子：
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影响因子：
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通讯作者：
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