Baruch-Shpigler Yael, Wang Huan, Tuvi-Arad Inbal, Avnir David
Institute of Chemistry, The Hebrew University of Jerusalem , Jerusalem 9190401, Israel.
Department of Natural Sciences, The Open University of Israel , Raanana 4353701, Israel.
Biochemistry. 2017 Oct 24;56(42):5635-5643. doi: 10.1021/acs.biochem.7b00525. Epub 2017 Sep 21.
Ramachandran plots (RPs) map the wealth of conformations of the polypeptide backbone and are widely used to characterize protein structures. A limitation of the RPs is that they are based solely on two dihedral angles for each amino acid residue and provide therefore only a partial picture of the conformational richness of the protein. Here we extend the structural RP analysis of proteins from a two-dimensional (2D) map to a three-dimensional map by adding the quantitative degree of chirality-the continuous chirality measure (CCM)-of the amino acid residue at each point in the RP. This measure encompasses all bond angles and bond lengths of an amino acid residue. We focus in this report on glycine (Gly) because, due to its flexibility, it occupies a large portion of the 2D map, thus allowing a detailed study of the chirality measure, and in order to evaluate the justification of classically labeling Gly as the only achiral amino acid. We have analyzed in detail 4366 Gly residues extracted from high resolution crystallographic data of 160 proteins. This analysis reveals not only that Gly is practically always conformationally chiral, but that upon comparing with the backbone of all amino acids, the quantitative chirality values of Gly are of similar magnitudes to those of the (chiral) amino acids. Structural trends and energetic considerations are discussed in detail. Generally we show that adding chirality to Ramachandran plots creates far more informative plots that highlight the sensitivity of the protein structure to minor conformational changes.
拉马钱德兰图（RPs）描绘了多肽主链丰富的构象，被广泛用于表征蛋白质结构。拉马钱德兰图的一个局限性在于，它们仅基于每个氨基酸残基的两个二面角，因此只能提供蛋白质构象丰富性的部分信息。在此，我们通过在拉马钱德兰图的每个点上增加氨基酸残基的手性定量程度——连续手性度量（CCM），将蛋白质的结构拉马钱德兰图分析从二维（2D）图扩展到三维图。该度量涵盖了氨基酸残基的所有键角和键长。在本报告中，我们聚焦于甘氨酸（Gly），因为由于其灵活性，它占据了二维图的很大一部分，从而便于对手性度量进行详细研究，并且为了评估将甘氨酸经典地标记为唯一无手性氨基酸的合理性。我们详细分析了从160种蛋白质的高分辨率晶体学数据中提取的4366个甘氨酸残基。该分析不仅揭示了甘氨酸实际上几乎总是构象性手性的，而且与所有氨基酸的主链相比，甘氨酸的定量手性值与（手性）氨基酸的定量手性值大小相似。我们还详细讨论了结构趋势和能量方面的考虑因素。总体而言，我们表明在拉马钱德兰图中加入手性会产生信息量大得多的图，突出了蛋白质结构对微小构象变化的敏感性。
