On evolutionary conservation of thermodynamic coupling in proteins
On evolutionary conservation of thermodynamic coupling in proteins
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DOI：
10.1074/jbc.m402560200
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发表时间：
2004-04-30
影响因子：
4.8
通讯作者：
Aldrich, RW
中科院分区：
文献类型：
--
作者：
Fodor, AA;Aldrich, RW
蛋白质中固有的热力学耦合的复杂性是理解蛋白质功能和工程蛋白质功能的主要挑战。最近的工作认为，通过使用进化记录中的相关突变来定位参与功能重要的、进化保守的能量途径的热力学耦合残基的一小部分，可以简化对蛋白质的研究。为了验证这一假设，我们检查了一些蛋白质的相关突变算法的预测，这些蛋白质的残基之间的耦合已经通过双突变循环的分析来确定。我们发现，相关突变算法可以找到物理上接近的残基对，并且物理上接近的残基对往往是热力学耦合的。然而，我们发现几乎没有证据支持热力学耦合限于进化约束的残基位置子集的假设。
The inherent complexity of thermodynamic coupling in proteins presents a major challenge in understanding and engineering protein function. Recent work has argued that the study of proteins can be simplified by the use of correlated mutations in the evolutionary record to locate a small subset of thermodynamically coupled residues that participate in functionally important, evolutionarily conserved energetic pathways. To test this hypothesis, we examined the predictions of correlated mutation algorithms for a number of proteins for which coupling between residues has been determined by analysis of double mutant cycles. We find that correlated mutation algorithms can find residue pairs that are physically close and that physically close residue pairs tend to be thermodynamically coupled. We find little evidence, however, for the hypothesis that thermodynamic coupling is limited to the subset of evolutionarily constrained residue positions.