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首页> 外文期刊>The journal of physical chemistry, A. Molecules, spectroscopy, kinetics, environment, & general theory >Assessing the Role of Polarization in Docking
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Assessing the Role of Polarization in Docking

机译：评估极化在对接中的作用

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We describe a strategy for including ligand and protein polarization in docking that is based on the conversion of induced dipoles to induced charges. Induced charges have a distinct advantage in that they are readily implemented into a number of different computer programs, including many docking programs and hybrid QM/MM programs; induced charges are also more readily interpreted. In this study, the ligand was treated quantum mechanically to avoid parametrization issues and was polarized by the target protein, which was treated as a set of point charges. The induced dipole at a given target atom, due to polarization by the ligand and neighboring residues, was reformulated as induced charges at the given atom and its bonded neighbors, and these were allowed to repolarize the ligand in an iterative manner. The final set of polarized charges was evaluated in docking using AutoDock 4.0 on 12 protein—ligand systems against the default empirical Gasteiger charges, and against nonpolarized and partially polarized potential-derived charges. One advantage of AutoDock is that the best rmsd structure can be identified not only from the lowest energy pose but also from the largest cluster of poses. Inclusion of polarization does not always lead to the lowest energy pose having a lower rmsd, because docking is designed by necessity to be rapid rather than accurate. However, whenever an improvement in methodology, corresponding to a more thorough treatment of polarization, resulted in an increased cluster size, then there was also a corresponding decrease in the rmsd. The options for implementing polarization within a purely classical docking framework are discussed.2008112
机译：我们描述了基于对偶极子到感应电荷的转换，在对接中包括配体和蛋白质极化的策略。感应电荷具有明显的优势，因为它们可以很容易地实现到许多不同的计算机程序中，包括许多对接程序和QM / MM混合程序。感应电荷也更容易解释。在这项研究中，对配体进行了量子力学处理，以避免参数化问题，并被靶蛋白极化，将其视为一组点电荷。由于配体和邻近残基的极化，在给定目标原子上的诱导偶极子被重新配制为在给定原子及其键合的邻近分子上的诱导电荷，并允许它们以迭代方式重新极化配体。使用AutoDock 4.0在12个蛋白质-配体系统上对接时，根据默认的经验Gasteiger电荷以及非极化和部分极化的电位衍生电荷，评估了最后一组极化电荷。 AutoDock的优点之一是，不仅可以从最低的能量姿态中识别出最佳的rmsd结构，而且可以从最大的姿态簇中识别出。包含极化并不总是导致最低的能量姿势具有较低的rmsd，因为对接必须根据需要进行快速设计，而不是精确设计。但是，只要方法上的改进（对应于更彻底的极化处理）导致簇尺寸增加，均方根值就会相应降低。讨论了在纯经典对接框架内实现极化的选项。2008112

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