Department of Life Sciences, University of Modena and Reggio Emilia, Via Campi 183, 41125, Modena, Italy.
J Am Chem Soc. 2012 Aug 22;134(33):13670-8. doi: 10.1021/ja3030356. Epub 2012 Aug 9.
Dynamic protein-solvent interactions are fundamental for life processes, but their investigation is still experimentally very demanding. Molecular dynamics simulations up to hundreds of nanoseconds can bring to light unexpected events even for extensively studied biomolecules. This paper reports a combined computational/experimental approach that reveals the reversible opening of two distinct fluctuating cavities in Saccharomyces cerevisiae iso-1-cytochrome c. Both channels allow water access to the heme center. By means of a mixed quantum mechanics/molecular dynamics (QM/MD) theoretical approach, the perturbed matrix method (PMM), that allows to reach long simulation times, changes in the reduction potential of the heme Fe(3+)/Fe(2+) couple induced by the opening of each cavity are calculated. Shifts of the reduction potential upon changes in the hydration of the heme propionates are observed. These variations are relatively small but significant and could therefore represent a tool developed by cytochrome c for the solvent driven, fine-tuning of its redox functionality.
动态蛋白质-溶剂相互作用是生命过程的基础，但它们的研究在实验上仍然非常具有挑战性。即使对于经过广泛研究的生物分子，分子动力学模拟也可以揭示数百纳秒的意想不到的事件。本文报道了一种结合计算/实验的方法，该方法揭示了酿酒酵母同工型 1-细胞色素 c 中两个独特的波动腔的可逆开放。这两个通道都允许水进入血红素中心。通过混合量子力学/分子动力学 (QM/MD) 理论方法，即允许达到长模拟时间的受扰矩阵方法 (PMM)，计算了每个腔打开时血红素 Fe(3+)/Fe(2+) 配合物还原电势的变化。观察到血红素丙酸盐水合变化时还原电势的偏移。这些变化虽然相对较小但却很显著，因此可能代表细胞色素 c 为溶剂驱动的精细调节其氧化还原功能而开发的一种工具。
