Machuqueiro Miguel, Baptista António M
Instituto de Tecnologia Química e Biológica, Universidade Nova de Lisboa, Av. da República, EAN, 2780-157 Oeiras, Portugal.
J Am Chem Soc. 2009 Sep 9;131(35):12586-94. doi: 10.1021/ja808463e.
Here we present a new implementation and extension of the stochastic titration method which makes it possible to perform MD simulations at constant pH and reduction potential. The method was applied to the redox titration of cytochrome c(3) from Desulfovibrio vulgaris Hildenborough, and a major finding of this study was that the method showed a better performance when the protein region is assigned a high dielectric constant. This dependence on the value of the protein dielectric constant was not found in previous constant-pH MD simulations and is attributed to excessively high heme-heme interactions at low dielectric constants. The simulations revealed strong coupling between hemes in close proximity, and we also showed how these couplings can be used to estimate the sensibility of the heme reductions to small pH changes.
在此我们展示了随机滴定法的一种新实现方式及扩展，该方法使得在恒定pH值和还原电位下进行分子动力学（MD）模拟成为可能。该方法应用于来自普通脱硫弧菌希登伯勒菌株的细胞色素c(3)的氧化还原滴定，本研究的一个主要发现是，当给蛋白质区域指定高介电常数时，该方法表现更佳。在先前的恒定pH值MD模拟中未发现这种对蛋白质介电常数的依赖性，这归因于低介电常数下血红素 - 血红素相互作用过高。模拟揭示了紧密相邻的血红素之间存在强耦合，并且我们还展示了如何利用这些耦合来估计血红素还原对微小pH变化的敏感性。
