Liu Xinsheng, Li Jing, Guo Wanlin, Wang Wei
Institute of Nanoscience, Nanjing University of Aeronautics and Astronautics, Nanjing 210016, China.
Biochem Biophys Res Commun. 2006 Dec 29;351(4):1031-6. doi: 10.1016/j.bbrc.2006.10.157. Epub 2006 Nov 7.
The conservation of residues in columns of a multiple sequence alignment (MSA) reflects the importance of these residues for maintaining the structure and function of a protein. To date, many scores have been suggested for quantifying residue conservation, but none has achieved the full rigor both in biology and statistics. In this paper, we present a new approach for measuring the evolutionary conservation at aligned positions. Our conservation measure is related to the logarithmic probabilities for aligned positions, and combines the physicochemical properties and the frequencies of amino acids. Such a measure is both biologically and statistically meaningful. For testing the relationship between an amino acid's evolutionary conservation and its role in the Phi-value defined protein folding kinetics, our results indicate that the folding nucleus residues may not be significantly more conserved than other residues by using the biological-relevance weighted statistical scoring method suggested in this paper as an alternative to entropy-based procedures.
多序列比对（MSA）中各列残基的保守性反映了这些残基对于维持蛋白质结构和功能的重要性。迄今为止，已经提出了许多用于量化残基保守性的评分方法，但没有一种在生物学和统计学上都达到完全严格的程度。在本文中，我们提出了一种测量比对位置上进化保守性的新方法。我们的保守性度量与比对位置的对数概率相关，并结合了氨基酸的物理化学性质和频率。这样的度量在生物学和统计学上都具有意义。为了测试氨基酸的进化保守性与其在Phi值定义的蛋白质折叠动力学中的作用之间的关系，我们的结果表明，通过使用本文提出的与生物学相关性加权的统计评分方法作为基于熵的程序的替代方法，折叠核心残基可能并不比其他残基更具显著的保守性。
