Electrostatic component of binding energy: Interpreting predictions from poisson-boltzmann equation and modeling protocols.
Electrostatic component of binding energy: Interpreting predictions from poisson-boltzmann equation and modeling protocols.
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DOI：
10.1002/jcc.24475
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发表时间：
2016-10-30
影响因子：
3
通讯作者：
Alexov, Emil
中科院分区：
文献类型：
--
作者：
Chakavorty, Arghya;Li, Lin;Alexov, Emil
大分子相互作用对于理解许多生物过程是必不可少的，并且通常由结合自由能表征。结合自由能的重要组成部分是静电，其经常通过泊松-玻尔兹曼方程（PBE）的解来建模。然而，大量的工作表明，结合自由能的静电分量（ΔΔ GdR）对所使用的参数和建模协议非常敏感。这促使一些研究人员质疑PBE在预测ΔΔ GdR方面的稳健性。我们认为，使用不同的输入参数和定义与PBE计算的绝对ΔΔ GdR的灵敏度并不表明PBE不足，而是应该预期的。我们展示了如何解释的明显的敏感性，在几个众多的物理参数的基本变化。我们表明，PBE方法是强大的每个考虑力场（CHARMM-27，AMBER-94和OPLS-AA），一旦相应的结构能量最小化。尽管使用了两种不同的分子表面定义，这一观察结果仍然成立，再次指出PBE在特定力场内提供了一致的结果。如果使用不同的建模协议计算，PBE递送的ΔΔ GdR值可能不同的事实不是PBE的缺陷，而是力场参数和能量最小化的势函数的差异的自然结果。此外，虽然使用不同力场计算的绝对ΔΔ GdR值不同，但它们的排序实际上保持相同，从而尽管使用了力场，也可以保持一致的排名。隐式溶剂模型的Poisson -Boltzmann框架提供了对各种物理和数值输入参数敏感的结果。然而，这不应被解释为它的弱点。重点是这些变化表明，当考虑不同的力场，最小化的程度和介电分配的方法。所有这些解释都是根据二元蛋白质复合物结合能ΔΔ GdR的静电分量来进行的。
Macromolecular interactions are essential for understanding numerous biological processes and are typically characterized by the binding free energy. Important component of the binding free energy is the electrostatics, which is frequently modeled via the solutions of the Poisson-Boltzmann Equations (PBE). However, numerous works have shown that the electrostatic component (ΔΔGelec) of binding free energy is very sensitive to the parameters used and modeling protocol. This prompted some researchers to question the robustness of PBE in predicting ΔΔGelec. We argue that the sensitivity of the absolute ΔΔGelec calculated with PBE using different input parameters and definitions does not indicate PBE deficiency, rather this is what should be expected. We show how the apparent sensitivity should be interpreted in terms of the underlying changes in several numerous and physical parameters. We demonstrate that PBE approach is robust within each considered force field (CHARMM-27, AMBER-94 and OPLS-AA) once the corresponding structures are energy minimized. This observation holds despite of using two different molecular surface definitions, pointing again that PBE delivers consistent results within particular force field. The fact that PBE delivered ΔΔGelec values may differ if calculated with different modeling protocols is not a deficiency of PBE, but natural results of the differences of the force field parameters and potential functions for energy minimization. In addition, while the absolute ΔΔGelec values calculated with different force field differ, their ordering remains practically the same allowing for consistent ranking despite of the force field used. Poisson –Boltzmann framework for implicit solvent models deliver results that are sensitive to various physical and numerical input parameters. This should not, however, be interpreted as its weakness. Emphasis is given on what these variations indicate when one considers different force fields, extents of minimization and method of dielectric assignment. All these interpretations are made in terms of the electrostatic component of binding energy ΔΔGelec of binary protein complexes.
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