On the polarization of ligands by proteins.
On the polarization of ligands by proteins.
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DOI：
10.1039/d0cp00376j
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发表时间：
2020-06-04
期刊：
影响因子：
--
通讯作者：
Minh DDL
中科院分区：
文献类型：
--
作者：
Willow SY;Xie B;Lawrence J;Eisenberg RS;Minh DDL
尽管许多蛋白质中的配体结合位点含有高密度的带电侧链，这些侧链可以使小有机分子极化并影响结合，但这种影响的大小尚未在许多系统中得到研究。本文采用量子力学/分子力学（QM/MM）方法，以配体为QM区，计算了PDBBind Core Set（2016年发布）中286种蛋白质-配体复合物的配体极化能。在有隐式溶剂和无隐式溶剂的情况下，基于域分解类导体筛选模型进行了计算。我们观察到配体极化能与作用在配体上的电场大小、诱导偶极矩大小和经典极化能呈线性相关。蛋白质和阳离子电荷对配体极化的影响随着距离的增加而减小，在9 Å和12 Å分别低于2 kcal/mol和1 kcal/mol。与这些嵌入场电荷相比，隐式溶剂对配体极化的影响相对较小。在计算某些晶体学配合物的负结合能时，同时考虑极化和溶剂化似乎是必要的。溶剂化，而不是极化，是实现与实验束缚自由能适度相关的必要条件。
Although ligand-binding sites in many proteins contain a high number density of charged side chains that can polarize small organic molecules and influence binding, the magnitude of this effect has not been studied in many systems. Here, we use a quantum mechanics/molecular mechanics (QM/MM) approach, in which the ligand is the QM region, to compute the ligand polarization energy of 286 protein-ligand complexes from the PDBBind Core Set (release 2016). Calculations were performed both with and without implicit solvent based on the domain decomposition Conductor–like Screening Model. We observe that the ligand polarization energy is linearly correlated with the magnitude of the electric field acting on the ligand, the magnitude of the induced dipole moment, and the classical polarization energy. The influence of protein and cation charges on the ligand polarization diminishes with the distance and is below 2 kcal/mol at 9 Å and 1 kcal/mol at 12 Å. Compared to these embedding field charges, implicit solvent has a relatively minor effect on ligand polarization. Considering both polarization and solvation appears essential to computing negative binding energies in some crystallographic complexes. Solvation, but not polarization, is essential for achieving moderate correlation with experimental binding free energies.
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