Redox potentials of protein disulfide bonds from free-energy calculations.
Redox potentials of protein disulfide bonds from free-energy calculations.
复制标题
DOI：
10.1021/acs.jpcb.5b01051
复制
发表时间：
2015-04
期刊：
影响因子：
--
通讯作者：
Wenjin Li;I. Baldus;F. Gräter
中科院分区：
文献类型：
--
作者：
Wenjin Li;I. Baldus;F. Gräter
蛋白质中的巯基/二硫键交换是所有生物体中的重要过程。为了确保特异性，所涉及的热力学和动力学被认为是由承载巯基/二硫键对的蛋白质的结构和动力学定制的。我们在这里的目的是预测蛋白质中的巯基/二硫键对的热力学。我们设计了一个自由能计算方案，它利用克鲁克斯高斯交叉法估计的氧化还原电位的巯基/二硫键对在12个蛋白质属于硫氧还蛋白超家族，即硫氧还蛋白，谷氧还蛋白，巯基-二硫键氧化还原酶在二硫键形成系统。我们得到了一个令人满意的计算与实验氧化还原电位（变化160 mV）的相关性，残差为1040 mV（8 kJ/mol），这大大减少时，考虑一个不太多样化的一组只有硫氧还蛋白。我们的简单和可转移的方法提供了一种途径，估计任何含二硫键的蛋白质的氧化还原电位，因为它的（还原或氧化）结构是已知的，从而代表了一个合理的设计氧化还原蛋白质的一步。
Thiol/disulfide exchange in proteins is a vital process in all organisms. To ensure specificity, the involved thermodynamics and kinetics are believed to be tailored by the structure and dynamics of the protein hosting the thiol/disulfide pair. We here aim at predicting the thermodynamics of thiol/disulfide pairs in proteins. We devise a free-energy calculation scheme, which makes use of the Crooks Gaussian intersection method to estimate the redox potential of thiol/disulfide pairs in 12 proteins belonging to the thioredoxin superfamily, namely, thioredoxins, glutaredoxins, and thiol-disulfide oxidoreductases in disulfide bond formation systems. We obtained a satisfying correlation of computed with experimental redox potentials (varying by 160 mV), with a residual error of ∼40 mV (8 kJ/mol), which drastically reduces when considering a less diverse set of only thioredoxins. Our simple and transferrable approach provides a route toward estimating redox potentials of any disulfide-containing protein given that its (reduced or oxidized) structure is known and thereby represents a step toward a rational design of redox proteins.