Sheng Yan-Jing, Yin Yue-Wen, Ma Yu-Qiang, Ding Hong-Ming
Center for Soft Condensed Matter Physics and Interdisciplinary Research, School of Physical Science and Technology, Soochow University, Suzhou 215006, China.
National Laboratory of Solid State Microstructures and Department of Physics, Collaborative Innovation Center of Advanced Microstructures, Nanjing University, Nanjing 210093, China.
J Chem Inf Model. 2021 May 24;61(5):2454-2462. doi: 10.1021/acs.jcim.1c00410. Epub 2021 May 3.
Accurate calculation of protein-protein binding free energy is of great importance in biological and medical science, yet it remains a hugely challenging problem. In this work, we develop a new strategy in which a screened electrostatic energy (i.e., adding an exponential damping factor to the Coulombic interaction energy) is used within the framework of the molecular mechanics/Poisson-Boltzmann surface area (MM/PBSA) method. Our results show that the Pearson correlation coefficient in the modified MM/PBSA is over 0.70, which is much better than that in the standard MM/PBSA, especially in the Amber14SB force field. In particular, the performance of the standard MM/PBSA is very poor in a system where the proteins carry like charges. Moreover, we also calculated the mean absolute error (MAE) between the calculated and experimental Δ values and found that the MAE in the modified MM/PBSA was indeed much smaller than that in the standard MM/PBSA. Furthermore, the effect of the dielectric constant of the proteins and the salt conditions on the results was also investigated. The present study highlights the potential power of the modified MM/PBSA for accurately predicting the binding energy in highly charged biosystems.
准确计算蛋白质 - 蛋白质结合自由能在生物和医学科学中具有极其重要的意义，但它仍然是一个极具挑战性的问题。在这项工作中，我们开发了一种新策略，即在分子力学/泊松 - 玻尔兹曼表面积（MM/PBSA）方法的框架内使用一种筛选静电能（即在库仑相互作用能上添加一个指数阻尼因子）。我们的结果表明，改进后的MM/PBSA中的皮尔逊相关系数超过0.70，这比标准MM/PBSA中的要好得多，尤其是在Amber14SB力场中。特别是，在蛋白质带有相同电荷的系统中，标准MM/PBSA的性能非常差。此外，我们还计算了计算值与实验Δ值之间的平均绝对误差（MAE），发现改进后的MM/PBSA中的MAE确实比标准MM/PBSA中的小得多。此外，还研究了蛋白质的介电常数和盐条件对结果的影响。本研究突出了改进后的MM/PBSA在准确预测高电荷生物系统中结合能方面的潜在能力。
