Yan Yuna, Yang Maoyou, Ji Chang G, Zhang John Z H
State Key Laboratory for Precision Spectroscopy, School of Chemistry and Molecular Engineering, East China Normal University , Shanghai 200062, China.
College of Mathematics & Physics, Shandong Institute of Light Industry , Jinan, Shandong 250353, China.
J Chem Inf Model. 2017 May 22;57(5):1112-1122. doi: 10.1021/acs.jcim.6b00734. Epub 2017 Apr 27.
The theoretical calculation of protein-protein binding free energy is a grand challenge in computational biology. Accurate prediction of critical residues along with their specific and quantitative contributions to protein-protein binding free energy is extremely helpful to reveal binding mechanisms and identify drug-like molecules that alter protein-protein interactions. In this paper, we propose an interaction entropy approach combined with the molecular mechanics/generalized Born surface area (MM/GBSA) method for solvation to compute residue-specific protein-protein binding free energy. In the current approach, the entropic loss in binding free energy of individual residues is explicitly computed from moledular dynamics (MD) simulation by using the interaction entropy method. In this approach the entropic contribution to binding free energy is determined from fluctuation of the interaction in MD simulation. Studies for an extensive set of realistic protein-protein interaction systems showed that by including the entropic contribution, the computed residue-specific binding free energies are in better agreement with the corresponding experimental data.
蛋白质-蛋白质结合自由能的理论计算是计算生物学中的一项重大挑战。准确预测关键残基及其对蛋白质-蛋白质结合自由能的特定和定量贡献，对于揭示结合机制以及识别改变蛋白质-蛋白质相互作用的类药物分子极为有用。在本文中，我们提出了一种结合分子力学/广义玻恩表面积（MM/GBSA）溶剂化方法的相互作用熵方法，用于计算残基特异性蛋白质-蛋白质结合自由能。在当前方法中，通过使用相互作用熵方法，从分子动力学（MD）模拟中明确计算单个残基结合自由能中的熵损失。在这种方法中，结合自由能的熵贡献由MD模拟中相互作用的波动确定。对大量实际蛋白质-蛋白质相互作用系统的研究表明，通过纳入熵贡献，计算得到的残基特异性结合自由能与相应的实验数据更吻合。
