Centro de Química e Bioquímica and Departamento de Química e Bioquímica, Faculdade de Ciências, Universidade de Lisboa, 1749-016 Lisboa, Portugal.
J Phys Chem B. 2013 Jan 10;117(1):70-82. doi: 10.1021/jp3082134. Epub 2012 Dec 19.
We studied the effect of using different heme group charge parametrization methods and schemes (Merz-Kollman, CHELPG, and single- and multiconformational RESP) on the quality of the results produced by the constant-(pH,E) MD method, applied to the redox titration of Desulfovibrio vulgaris Hildenborough cytochrome c(3). These new and more accurate charge sets enabled us to overcome the previously reported dependence of the method's performance on the dielectric constant, ε, assigned to the protein region. In particular, we found a systematic, clear shift of the E(mod) toward more negative values than those previously reported, in agreement with an electrostatics based reasoning. The simulations showed strong coupling between protonating/redox sites. We were also able to capture significant direct and, especially, indirect interactions between hemes, such as those mediated by histidine 67. Our results highlight the importance of having a good quantum description of the system before deriving atomic partial charges for classic force fields.
我们研究了使用不同的血红素基团电荷参数化方法和方案（Merz-Kollman、 CHELPG、单和多构象 RESP）对恒（pH，E）MD 方法应用于脱硫弧菌 Hildenborough 细胞色素 c(3)氧化还原滴定所产生结果质量的影响。这些新的、更准确的电荷集使我们能够克服以前报道的该方法的性能对分配给蛋白质区域的介电常数 ε 的依赖性。特别是，我们发现 E(mod)系统地向比以前报道的更负的值偏移，这与基于静电的推理一致。模拟显示质子化/氧化还原位点之间存在强烈的耦合。我们还能够捕捉到血红素之间的显著直接和（特别是）间接相互作用，例如由组氨酸 67 介导的相互作用。我们的结果强调了在为经典力场推导原子部分电荷之前对系统进行良好量子描述的重要性。
