Göbel U, Sander C, Schneider R, Valencia A
Protein Design Group, European Molecular Biology Laboratory, Heidelberg, Germany.
Proteins. 1994 Apr;18(4):309-17. doi: 10.1002/prot.340180402.
The maintenance of protein function and structure constrains the evolution of amino acid sequences. This fact can be exploited to interpret correlated mutations observed in a sequence family as an indication of probable physical contact in three dimensions. Here we present a simple and general method to analyze correlations in mutational behavior between different positions in a multiple sequence alignment. We then use these correlations to predict contact maps for each of 11 protein families and compare the result with the contacts determined by crystallography. For the most strongly correlated residue pairs predicted to be in contact, the prediction accuracy ranges from 37 to 68% and the improvement ratio relative to a random prediction from 1.4 to 5.1. Predicted contact maps can be used as input for the calculation of protein tertiary structure, either from sequence information alone or in combination with experimental information.
蛋白质功能和结构的维持限制了氨基酸序列的进化。这一事实可用于将序列家族中观察到的相关突变解释为三维空间中可能存在物理接触的指示。在此，我们提出一种简单通用的方法来分析多序列比对中不同位置间突变行为的相关性。然后，我们利用这些相关性预测11个蛋白质家族各自的接触图，并将结果与晶体学确定的接触情况进行比较。对于预测有接触的相关性最强的残基对，预测准确率在37%至68%之间，相对于随机预测的提升率在1.4至5.1之间。预测的接触图可作为计算蛋白质三级结构的输入，既可以仅根据序列信息，也可以结合实验信息来进行计算。
