Fragment-based quantum mechanical calculation of protein-protein binding affinities,Journal of Computational Chemistry

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Fragment-based quantum mechanical calculation of protein-protein binding affinities
Journal of Computational Chemistry ( IF 3.4 ) Pub Date : 2018-04-29 , DOI: 10.1002/jcc.25236
Yaqian Wang ₁ , Jinfeng Liu _{1,

2} , Jinjin Li ₃ , Xiao He _{1,

4,

5}

Affiliation

The electrostatically embedded generalized molecular fractionation with conjugate caps (EE‐GMFCC) method has been successfully utilized for efficient linear‐scaling quantum mechanical (QM) calculation of protein energies. In this work, we applied the EE‐GMFCC method for calculation of binding affinity of Endonuclease colicin–immunity protein complex. The binding free energy changes between the wild‐type and mutants of the complex calculated by EE‐GMFCC are in good agreement with experimental results. The correlation coefficient (R) between the predicted binding energy changes and experimental values is 0.906 at the B3LYP/6‐31G*‐D level, based on the snapshot whose binding affinity is closest to the average result from the molecular mechanics/Poisson–Boltzmann surface area (MM/PBSA) calculation. The inclusion of the QM effects is important for accurate prediction of protein–protein binding affinities. Moreover, the self‐consistent calculation of PB solvation energy is required for accurate calculations of protein–protein binding free energies. This study demonstrates that the EE‐GMFCC method is capable of providing reliable prediction of relative binding affinities for protein–protein complexes. © 2018 Wiley Periodicals, Inc.

中文翻译：

基于片段的蛋白质-蛋白质结合亲和力的量子力学计算

具有共轭帽的静电嵌入广义分子分级（EE-GMFCC）方法已成功用于蛋白质能量的有效线性标度量子力学（QM）计算。在这项工作中，我们应用 EE-GMFCC 方法计算核酸内切酶大肠杆菌素-免疫蛋白复合物的结合亲和力。EE-GMFCC 计算的复合物野生型和突变体之间的结合自由能变化与实验结果非常吻合。基于结合亲和力最接近分子力学/泊松-玻尔兹曼平均结果的快照，预测结合能变化与实验值之间的相关系数 (R) 在 B3LYP/6-31G*-D 水平为 0.906表面积 (MM/PBSA) 计算。包含 QM 效应对于准确预测蛋白质 - 蛋白质结合亲和力很重要。此外，精确计算蛋白质-蛋白质结合自由能需要PB溶剂化能的自洽计算。该研究表明，EE-GMFCC 方法能够可靠地预测蛋白质-蛋白质复合物的相对结合亲和力。© 2018 Wiley Periodicals, Inc.

更新日期：2018-04-29

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