Department of Bioinformatics, School of Life Sciences, Bharathidasan University, Tiruchirappalli, TN 620024, India.
Protein Eng Des Sel. 2010 Dec;23(12):911-8. doi: 10.1093/protein/gzq070. Epub 2010 Oct 15.
Protein folding is a natural phenomenon by which a sequence of amino acids folds into a unique functional three-dimensional structure. Although the sequence code that governs folding remains a mystery, one can identify key inter-residue contacts responsible for a given topology. In nature, there are many pairs of proteins of a given length that share little or no sequence identity. Similarly, there are many proteins that share a common topology but lack significant evidence of homology. In order to tackle this problem, protein engineering studies have been used to determine the minimal number of amino acid residues that codes for a particular fold. In recent years, the coupling of theoretical models and experiments in the study of protein folding has resulted in providing some fruitful clues. He et al. have designed two proteins with 88% sequence identity, which adopt different folds and functions. In this work, we have systematically analysed these two proteins by performing pentapeptide search, secondary structure predictions, variation in inter-residue interactions and residue-residue pair preferences, surrounding hydrophobicity computations, conformational switching and energy computations. We conclude that the local secondary structural preference of the two designed proteins at the Nand C-terminal ends to adopt either coil or strand conformation may be a crucial factor in adopting the different folds. Early on during the process of folding, both proteins may choose different energetically favourable pathways to attain the different folds.
蛋白质折叠是一种自然现象，其中氨基酸序列折叠成独特的功能三维结构。尽管控制折叠的序列代码仍然是一个谜，但人们可以识别出负责特定拓扑结构的关键残基间接触。在自然界中，有许多长度相同但序列相似性很小或没有的蛋白质对。同样，有许多蛋白质具有共同的拓扑结构，但缺乏同源性的明显证据。为了解决这个问题，蛋白质工程研究已被用于确定编码特定折叠的最小氨基酸残基数。近年来，理论模型与蛋白质折叠研究中的实验相结合，为解决这一问题提供了一些有益的线索。何等人设计了两个具有 88%序列相似性的蛋白质，它们采用不同的折叠和功能。在这项工作中，我们通过进行五肽搜索、二级结构预测、残基间相互作用和残基对偏好的变化、周围疏水性计算、构象转换和能量计算，对这两种蛋白质进行了系统分析。我们得出的结论是，两种设计的蛋白质在 N 端和 C 端采用卷曲或链构象的局部二级结构偏好可能是采用不同折叠的关键因素。在折叠过程的早期，两种蛋白质可能会选择不同的能量有利途径来获得不同的折叠。
