Warwicker J
Protein Engineering Department, AFRC Institute of Food Research Reading Laboratory, U.K.
J Mol Biol. 1994 Feb 25;236(3):887-903. doi: 10.1006/jmbi.1994.1196.
Electrostatic interactions in macromolecules can be calculated with the method of finite differences applied to a continuum model. The accuracy of dielectric and counterion continuum modelling has been tested for long-range interactions by comparison with available experimental data over a range of ionic strengths. Various model parameters have been adjusted. Some have little effect, such as protein dielectric and the selection of Van der Waals radii. It is shown that the reduction in interaction due to dielectric effects is overestimated when a dielectric constant of 80 is assigned to all solvent accessible regions. Improved agreement is seen when the effects of the Kirkwood correlation sphere and dielectric saturation are included. Further support for the use of dielectric saturation arises from a correlation of solvent polarization saturation with crystallographic ordered water structure. Calculations over the medium ionic strength range indicate that requiring counterions to maintain a solvent layer places too great a restriction on their approach to the protein-solvent interface. However, counterion accessibility that coincides with the solvent accessible region gives too much interaction damping. Modelling of observed ion binding sites suggests that a counterion response which includes an ion desolvation term, obtained by difference calculation, will improve the computation of ionic strength effects. This study demonstrates that there is scope for improvement in continuum electrostatics calculations, and shows that progress is possible with the inclusion of physically realistic solvent and counterion properties at the protein surface.
大分子中的静电相互作用可以通过应用于连续介质模型的有限差分法来计算。通过与一系列离子强度下的现有实验数据进行比较，已对介电和抗衡离子连续介质模型在长程相互作用方面的准确性进行了测试。对各种模型参数进行了调整。有些参数影响很小，例如蛋白质介电常数和范德华半径的选择。结果表明，当将介电常数80赋予所有溶剂可及区域时，由于介电效应导致的相互作用降低被高估了。当考虑柯克伍德相关球和介电饱和效应时，一致性得到了改善。溶剂极化饱和与晶体学有序水结构的相关性进一步支持了介电饱和的应用。在中等离子强度范围内的计算表明，要求抗衡离子维持溶剂层对其接近蛋白质 - 溶剂界面施加了过大的限制。然而，与溶剂可及区域重合的抗衡离子可及性给出了过多的相互作用阻尼。对观察到的离子结合位点的建模表明，通过差分计算获得的包括离子去溶剂化项的抗衡离子响应将改善离子强度效应的计算。这项研究表明，连续介质静电计算仍有改进的空间，并表明通过纳入蛋白质表面实际的溶剂和抗衡离子性质是可以取得进展的。
