Sham Y Y, Muegge I, Warshel A
Department of Chemistry, University of Southern California, Los Angeles 90089-1062, USA.
Biophys J. 1998 Apr;74(4):1744-53. doi: 10.1016/S0006-3495(98)77885-3.
The effect of the reorganization of the protein polar groups on charge-charge interaction and the corresponding effective dielectric constant (epsilon(eff)) is examined by the semimicroscopic version of the Protein Dipole Langevin Dipoles (PDLD/S) method within the framework of the Linear Response Approximation (LRA). This is done by evaluating the interactions between ionized residues in the reaction center of Rhodobacter sphaeroides, while taking into account the protein reorganization energy. It is found that an explicit consideration of the protein relaxation leads to a significant increase in epsilon(eff) and that semimicroscopic models that do not take this relaxation into account force one to use a large value for the so-called "protein dielectric constant," epsilon(p), of the Poisson-Boltzmann model or for the corresponding epsilon(in) in the PDLD/S model. An additional increase in epsilon(eff) is expected from the reorganization of ionized residues and from changes in the degree of water penetration. This finding provides further support for the idea that epsilon(in) (or epsilon(p)) represents contributions that are not considered explicitly. The present study also provides a systematic illustration of the nature of epsilon(eff), supporting our previously reported view that charge-charge interactions correspond to a large value of this "dielectric constant," even in protein interiors. It is also pointed out that epsilon(eff) for the interaction between ionizable groups in proteins is very different from the effective dielectric constant, epsilon'(eff), that determines the free energy of ion pairs in proteins (epsilon'(eff) reflects the effect of preoriented protein dipoles). Finally, the problems associated with the search for a general epsilon(in) are discussed. It is clarified that the epsilon(in) that reproduces the effect of protein relaxation on charge-charge interaction is not equal to the epsilon(in) that reproduces the corresponding effect upon formation of individual charges. This reflects fundamental inconsistencies in attempts to cast microscopic concepts in a macroscopic model. Thus one should either use a large epsilon(in) for charge-charge interactions and a small epsilon(in) for charge-dipole interactions or consider the protein relaxation microscopically.
在线性响应近似（LRA）框架内，通过蛋白质偶极朗之万偶极子（PDLD/S）方法的半微观版本，研究了蛋白质极性基团重组对电荷 - 电荷相互作用及相应有效介电常数（εeff）的影响。通过评估球形红杆菌反应中心中离子化残基之间的相互作用来实现这一点，同时考虑蛋白质重组能。研究发现，明确考虑蛋白质弛豫会导致εeff显著增加，而未考虑这种弛豫的半微观模型迫使人们在泊松 - 玻尔兹曼模型的所谓“蛋白质介电常数”εp或PDLD/S模型中的相应εin使用较大值。预计离子化残基的重组和水渗透程度的变化会使εeff进一步增加。这一发现为εin（或εp）代表未明确考虑的贡献这一观点提供了进一步支持。本研究还系统地阐述了εeff的性质，支持了我们之前报道的观点，即即使在蛋白质内部，电荷 - 电荷相互作用也对应于这个“介电常数”的较大值。还指出，蛋白质中可电离基团之间相互作用的εeff与决定蛋白质中离子对自由能的有效介电常数ε'eff非常不同（ε'eff反映了预取向蛋白质偶极子的影响）。最后，讨论了寻找通用εin相关的问题。明确了再现蛋白质弛豫对电荷 - 电荷相互作用影响的εin与再现单个电荷形成时相应影响的εin不相等。这反映了在将微观概念纳入宏观模型的尝试中存在的基本不一致性。因此，人们要么在电荷 - 电荷相互作用中使用较大的εin，在电荷 - 偶极相互作用中使用较小的εin，要么从微观角度考虑蛋白质弛豫。
