Effect of the Asn52----Ile mutation on the redox potential of yeast cytochrome c. Theory and experiment.
Effect of the Asn52----Ile mutation on the redox potential of yeast cytochrome c. Theory and experiment.
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Asn52----Ile突变对酵母细胞色素c氧化还原电位的影响。
DOI：
10.1016/0022-2836(92)90546-v
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发表时间：
1992
影响因子：
5.6
通讯作者：
Warshel,A
中科院分区：
文献类型：
--
作者：
Langen,R;Brayer,GD;Berghuis,AM;McLendon,G;Sherman,F;Warshel,A
本文以细胞色素Asn 52 → Ile突变为例，研究了电子传递蛋白质序列变化与氧化还原电位相关性的理论方法。第一种方法使用蛋白质偶极子Langevin偶极子（PDLD）方法和高分辨率的X-射线结构的天然和突变蛋白质。这种方法被发现给可靠的结果，所有的溶剂分子所代表的朗之万偶极子，也当一些束缚水分子表示明确。还发现自由能微扰法可以给出合理的结果，但代价是花费更多的计算机时间。最后，通过分子动力学模拟从天然结构产生突变结构，然后在PDLD计算中使用这些配置的方法被发现对相应的氧化还原电位的突变的效果给出了合理的估计。在这里和Phe 82 → Ser突变的初步测试案例中获得的令人鼓舞的结果表明，本策略可以为蛋白质中的结构-氧化还原和序列-氧化还原相关性提供有用的工具。
Theoretical methods for correlation of sequence changes and redox potential of electron transport proteins are examined using the Asn52 → Ile mutation in cytochromecas a test case. The first approach uses the protein dipoles Langevin dipoles (PDLD) method and the high resolution X-ray structures of the native and the mutant proteins. This approach is found to give reliable results where all the solvent molecules are represented by Langevin dipoles and also when some bound water molecules are represented explicitly. A free energy perturbation method is also found to give reasonable results but at the expense of much more computer time. Finally, an approach that generates mutant structures from the native structure by molecular dynamics simulation and then uses these configurations in PDLD calculations is found to give a reasonable estimate of the effect of the mutation on the corresponding redox potential. The encouraging results obtained here and in a preliminary test case of the Phe82 → Ser mutation indicates that the present strategies can provide a useful tool for structure-redox and sequence-redox correlation in proteins.