Charge optimization leads to favorable electrostatic binding free energy
Charge optimization leads to favorable electrostatic binding free energy
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DOI：
10.1103/physreve.59.5958
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发表时间：
1999-05-01
影响因子：
2.4
通讯作者：
Tidor, B
中科院分区：
文献类型：
--
作者：
Kangas, E;Tidor, B
分子静电电荷分布的变分优化是研究溶液中分子缔合反应的一种工具。原则上，这种方法可以用于药物设计和蛋白质折叠，以分析和改进分子相互作用，并为分子设计提供静电模板。这个最优化问题归结为经典静电学中的逆源问题，其中源由外极化势和自极化势的组合来确定。在这篇文章中，我们证明了在许多有物理意义的情况下，静电优化分子的自由缔合能的静电部分有一个为零的上限。也就是说，变分优化提供了配体-电荷分布，即使在强极性介质中也有利于结合的能量学。这种对缔合反应的稳定作用与静电在水溶液络合物中的通常作用相反，在水溶液络合物中，脱溶效应通常占主导地位。我们还证明了变分解的存在唯一性，并将其与静电像荷问题联系起来。[S1063-651X(99)08305-1]。
Variational optimization of molecular electrostatic charge distributions is a tool for the study of association reactions of molecules in solution. In principle,this method can be used in drug design and protein folding to analyze and improve molecular interactions and to provide electrostatic templates for molecular design. This optimization problem reduces to an inverse source problem in classical electrostatics, where the sources are determined by a combination of external and self-polarization potentials. In this paper, we show that the electrostatic portion of the free energy of association for electrostatically optimized molecules has an upper bound of zero in many situations of physical interest. That is, variational optimization provides a ligand-charge distribution that contributes favorably to the energetics of binding, even in a strongly polar medium. This stabilizing effect on association reactions is contrary to the usual role of electrostatics in aqueous complexes, in which desolvation effects generally dominate. We also show the existence and nonuniqueness of the variational solution and make a connection to the electrostatic image charge problem. [S1063-651X(99)08305-1].