The biomolecules interact with their partners in an aqueous media; thus, their solvation energy is an important thermodynamics quantity. In previous works (J. Chem. Theory Comput. 14(2): 1020–1032), we demonstrated that the Poisson–Boltzmann (PB) approach reproduces solvation energy calculated via thermodynamic integration (TI) protocol if the structures of proteins are kept rigid. However, proteins are not rigid bodies and computing their solvation energy must account for their flexibility. Typically, in the framework of PB calculations, this is done by collecting snapshots from molecular dynamics (MD) simulations, computing their solvation energies, and averaging to obtain the ensemble‐averaged solvation energy, which is computationally demanding. To reduce the computational cost, we have proposed Gaussian/super‐Gaussian‐based methods for the dielectric function that use the atomic packing to deliver smooth dielectric function for the entire computational space, the protein and water phase, which allows the ensemble‐averaged solvation energy to be computed from a single structure. One of the technical difficulties associated with the smooth dielectric function presentation with respect to polar solvation energy is the absence of a dielectric border between the protein and water where induced charges should be positioned. This motivated the present work, where we report a super‐Gaussian regularized Poisson–Boltzmann method and use it for computing the polar solvation energy from single energy minimized structures and assess its ability to reproduce the ensemble‐averaged polar solvation on a dataset of 74 high‐resolution monomeric proteins.

中文翻译：

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使用正则化超高斯泊松-玻尔兹曼模型从能量最小化结构中传递蛋白质的极性溶剂化自由能


生物分子在水性介质中与其伙伴相互作用;因此，它们的溶剂化能是一个重要的热力学量。在以前的工作 （J. Chem. Theory Comput. 14（2）： 1020–1032） 中，我们证明了如果蛋白质的结构保持刚性，泊松-玻尔兹曼 （PB） 方法可以再现通过热力学积分 （TI） 协议计算的溶剂化能。然而，蛋白质不是刚体，计算它们的溶剂化能必须考虑它们的灵活性。通常，在 PB 计算的框架中，这是通过从分子动力学 （MD） 模拟中收集快照，计算它们的溶剂化能，然后平均以获得集成平均的溶剂化能量来完成的，这对计算要求很高。为了降低计算成本，我们提出了基于高斯/超高斯的介电函数方法，该方法使用原子堆积为整个计算空间、蛋白质和水相提供平滑的介电函数，这允许从单个结构计算集成平均溶剂化能量。与极性溶剂化能的平滑介电函数表示相关的技术难题之一是蛋白质和水之间没有介电边界，感应电荷应位于该边界。这激发了目前的工作，我们报告了一种超高斯正则化泊松-玻尔兹曼方法，并将其用于计算来自单能最小化结构的极性溶剂化能，并评估其在 74 种高分辨率单体蛋白的数据集上再现集成平均极性溶剂化的能力。