Prediction of reorganization free energies for biological electron transfer: a comparative study of Ru-modified cytochromes and a 4-helix bundle protein.
Prediction of reorganization free energies for biological electron transfer: a comparative study of Ru-modified cytochromes and a 4-helix bundle protein.
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DOI：
10.1021/ja107876p
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发表时间：
2010-11
影响因子：
15
通讯作者：
V. Tipmanee;H. Oberhofer;Mina Park;Kwang Soo Kim;J. Blumberger
中科院分区：
文献类型：
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作者：
V. Tipmanee;H. Oberhofer;Mina Park;Kwang Soo Kim;J. Blumberger
氧化还原蛋白质相对于水性溶质的电子转移（ET）速率的加速可以归因于蛋白质在ET时降低核反应或重组的能力，同时保持足够高的电子耦合。重组自由能的定量预测仍然是一个挑战，无论是实验还是计算。使用密度泛函计算和分子动力学模拟与电子极化力场，我们报告重组自由能的蛋白质内ET在四个血红素含ET蛋白质，不同的蛋白质折叠，亲水性，和溶剂的可及性的电子接受组。ET从细胞色素c和B（5）的血红素辅因子到与这些蛋白质表面的组氨酸残基对接的暴露于溶剂的Ru复合物的重组自由能落在1.2-1.3 eV的窄范围内。重组自由能显着降低，在设计的4-螺旋束蛋白质，其中两个氧化还原活性辅因子被保护免受溶剂。对于所有研究的ET反应，重组的主要成分是溶剂和蛋白质，溶剂贡献接近或超过50%的总量。在四分之三的蛋白质中，蛋白质重组自由能可以被视为包括许多残基的集体效应，每个残基贡献很小的一部分。这些结果对人工电子传递蛋白的设计具有重要意义。他们认为，重组自由能可能在一般情况下不能有效地控制单点突变，但在很大程度上的溶剂暴露程度的电离辅因子。
The acceleration of electron transfer (ET) rates in redox proteins relative to aqueous solutes can be attributed to the protein's ability to reduce the nuclear response or reorganization upon ET, while maintaining sufficiently high electronic coupling. Quantitative predictions of reorganization free energy remain a challenge, both experimentally and computationally. Using density functional calculations and molecular dynamics simulation with an electronically polarizable force field, we report reorganization free energies for intraprotein ET in four heme-containing ET proteins that differ in their protein fold, hydrophilicity, and solvent accessibility of the electron-accepting group. The reorganization free energies for ET from the heme cofactors of cytochrome c and b(5) to solvent exposed Ru-complexes docked to histidine residues at the surface of these proteins fall within a narrow range of 1.2-1.3 eV. Reorganization free energy is significantly lowered in a designed 4-helix bundle protein where both redox active cofactors are protected from the solvent. For all ET reactions investigated, the major components of reorganization are the solvent and the protein, with the solvent contributing close to or more than 50% of the total. In three out of four proteins, the protein reorganization free energy can be viewed as a collective effect including many residues, each of which contributing a small fraction. These results have important implications for the design of artificial electron transport proteins. They suggest that reorganization free energy may in general not be effectively controlled by single point mutations, but to a large extent by the degree of solvent exposure of the ionizable cofactors.