Numerical calculations of the pH of maximal protein stability - The effect of the sequence composition and three-dimensional structure
Numerical calculations of the pH of maximal protein stability - The effect of the sequence composition and three-dimensional structure
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DOI：
10.1046/j.1432-1033.2003.03917.x
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发表时间：
2004-01-01
期刊：
影响因子：
--
通讯作者：
Alexov, E
中科院分区：
文献类型：
--
作者：
Alexov, E
研究了大量实验发现的具有最大稳定性的不同最适pH的蛋白质，以揭示它们对特定pH的偏好的基本原理。依赖于pH的折叠自由能被数值模拟为pH和蛋白质净电荷的函数。在数值计算中，确定最适pH为折叠自由能最小的pH。最稳定pH(实验最适pH)的实验数据重现性好(RMSD=0.73)。结果表明，最佳pH是由氨基酸组成和可滴定基团的三维结构组成两个因素决定的。结果表明，最适pH和等电点可以有很大的不同。在许多情况下，最适pH是在对应于蛋白质的大净电荷的pH时找到的。同时，具有酸性最佳PHS的蛋白质的碱酸比有小于1的趋势，反之亦然。如果只考虑埋藏组，则最适pH与碱酸比之间的相关性是显著的。研究表明，为酸提供有利的静电环境而不利于碱性的蛋白质往往具有较高的最适pH，反之亦然。
A large number of proteins, found experimentally to have different optimum pH of maximal stability, were studied to reveal the basic principles of their preferenence for a particular pH. The pH-dependent free energy of folding was modeled numerically as a function of pH as well as the net charge of the protein. The optimum pH was determined in the numerical calculations as the pH of the minimum free energy of folding. The experimental data for the pH of maximal stability (experimental optimum pH) was reproducible (rmsd = 0.73). It was shown that the optimum pH results from two factors - amino acid composition and the organization of the titratable groups with the 3D structure. It was demonstrated that the optimum pH and isoelectric point could be quite different. In many cases, the optimum pH was found at a pH corresponding to a large net charge of the protein. At the same time, there was a tendency for proteins having acidic optimum pHs to have a base/acid ratio smaller than one and vice versa. The correlation between the optimum pH and base/acid ratio is significant if only buried groups are taken into account. It was shown that a protein that provides a favorable electrostatic environment for acids and disfavors the bases tends to have high optimum pH and vice versa.