Prediction of functionally important residues based solely on the computed energetics of protein structure
Prediction of functionally important residues based solely on the computed energetics of protein structure
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DOI：
10.1006/jmbi.2001.5009
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发表时间：
2001-09-28
影响因子：
5.6
通讯作者：
Elcock, AH
中科院分区：
文献类型：
--
作者：
Elcock, AH
蛋白质中的催化和其他功能重要的残基通常可以突变以产生更稳定的蛋白质。这些残基中的许多是位于静电不利环境中的带电残基。在这里，它表明，因为连续静电方法可以识别这些不稳定的残基，同样的方法也可以用来识别功能上重要的残基，否则未表征的蛋白质。为了建立这一点，详细的计算进行了六个蛋白质，良好的结构和突变数据可从实验中获得。在所有情况下，研究表明，已知实验上不稳定的功能重要残基是计算中发现的最不稳定的残基之一。对216种不同蛋白质进行的更大规模的分析表明，带电残基的计算静电能与其进化保守程度之间存在一般关系。这种关系变得模糊时，静电能量计算库仑定律，而不是更完整的连续静电法。最后，在该方法的第一个预测应用中，对结构基因组学联盟最近报道的三种蛋白质进行计算。(C)北京：科学出版社.
Catalytic and other functionally important residues in proteins can often be mutated to yield more stable proteins. Many of these residues are charged residues that are located in electrostatically unfavorable environments. Here it is demonstrated that because continuum electrostatics methods can identify these destabilizing residues, the same methods can also be used to identify functionally important residues in otherwise uncharacterized proteins. To establish this point, detailed calculations are performed on six proteins for which good structural and mutational data are available from experiments. In all cases it is shown that functionally important residues known to be destabilizing experimentally are among the most destabilizing residues found in the calculations. A larger scale analysis performed on 216 different proteins demonstrates the existence of a general relationship between the calculated electrostatic energy of a charged residue and its degree of evolutionary conservation. This relationship becomes obscured when electrostatic energies are calculated using Coulomb's law instead of the more complete continuum electrostatics method. Finally, in a first predictive application of the method, calculations are performed on three proteins whose structures have recently been reported by a structural genomics consortium. (C) 2001 Academic Press.