论文标题
关于蛋白质配体极化
On the Polarization of Ligands by Proteins
论文作者
论文摘要
尽管许多蛋白质中的配体结合位点含有高数量的带电侧链密度，这些侧链可以极化小有机分子并影响结合，但在许多系统中尚未研究这种效果的大小。在这里，我们使用量子力学/分子力学（QM/mm）方法，其中配体是QM区域，用于计算PDBBIND核心的286蛋白质配体配合物的配体极化能（发行2016年）。我们观察到配体极化能与作用于配体上的电场的大小，诱导的偶极矩的大小和经典的极化能相关。蛋白质和阳离子电荷对配体极化的影响减少了距离，在9 $ \ unicode {x212b} $和12 $ \ unicode {x212b} $时的距离低于2 kcal/mol。考虑到极化和溶剂化似乎对于计算某些晶体学复合物中的负结合能至关重要。溶剂化而非极化对于与实验结合自由能中等相关性至关重要。
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). 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 $\unicode{x212B}$ and 1 kcal/mol at 12 $\unicode{x212B}$. 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.
