AI 中文总结
本文针对非刚性蛋白质极性溶剂化能计算问题，提出适配非刚性构象变化的广义PB框架，经多系统验证其准确性与鲁棒性。
AI 中文摘要
泊松-玻尔兹曼（PB）理论是用于静电分析的隐式溶剂模型的基石，已在多种生物分子应用中取得巨大成功。然而，在计算极性溶剂化能时，需考虑蛋白质从真空相转变为水相时结构会发生变化。为解决该问题，本文首次提出一种广义PB框架，可适配非刚性构象变化且不会出现自能伪影。对于正则化PB模型（其电荷奇异性由格林函数捕捉），水相和真空态的自能将被解析抵消；对于非正则化PB求解器（如APBS和DelPhi），本文提出一种简单的非刚性蛋白质热力学循环，通过在真空中添加库仑校正实现。该广义PB理论经受扰双原子系统及一组真空和水相中结构各异的多种蛋白质验证，无论选用尖锐界面还是弥散界面PB模型，以及不同数值求解器，均展现出准确性和鲁棒性。
英文摘要
The Poisson-Boltzmann (PB) theory is a cornerstone of implicit solvent models for electrostatic analysis, and has found a great success in various biomolecular applications. However, in calculating polar solvation energy, one should consider that the structure of the protein changes upon transition from vacuum to water phases. To address this, here we report for the first time a generalized PB framework capable of accommodating nonrigid conformational changes without suffering from self-energy artifacts. For regularized PB models, in which the charge singularities are captured by the Green's functions, self-energies in the water and vacuum states will be analytically canceled. For non-regularized PB solvers, such as APBS and DelPhi, a simple thermodynamic cycle is proposed for nonrigid proteins by adding a Coulombic correction in vacuum. The generalized PB theory is validated using a perturbed two-atom system and a diverse set of proteins with different structures in vacuum and water, demonstrating its accuracy and robustness, regardless of the choice of sharp-interface and diffuse-interface PB models and different numerical solvers.
Comments6 pages, 2 figures
