Serrano L
EMBL, Structure and Biocomputing Programme, Heidelberg, Germany.
J Mol Biol. 1995 Nov 24;254(2):322-33. doi: 10.1006/jmbi.1995.0619.
It has been indicated that amino acids have various intrinsic phi and psi propensities, as demonstrated from the comparison between experimental secondary structure propensities and their relative statistical distribution in the protein database for the appropriate region of the Ramachandran plot. However, this does not eliminate the possibility that these experimental propensities are the result of context effects due to the secondary structure environment of the mutated position. To demonstrate that there are at least real intrinsic phi propensities, independent of context effects, we have used two different nuclear magnetic resonance parameters related to the phi dihedral angle (J3 alpha HN coupling constants and the chemical shift of the C alpha H proton), determined in random-coil tetra- and pentapeptides, and/or in proteins. Comparison of the experimentally determined values for these parameters with the theoretical ones determined from the analysis by different empirical and theoretical equations of the phi dihedral angle statistical distribution of the amino acids in the protein database, supports the idea that each amino acid has, at least, different phi intrinsic propensities. Consideration of all conformations, or only coil conformations, in the protein database produces similar results. The reasonable correlation between these experimental and theoretical data and the hydrogen-exchange data in random-coil peptides suggests that maximisation of hydrophobic surface-buried and hydrogen-bond formation with the solvent could be responsible for these different random-coil conformational preferences. Analysis of the intrinsic propensities for beta-strand, alpha-helix and polyproline II dihedral angles of the 20 amino acids in coil conformations, indicates that the side-chain of the amino acids is mainly determining the relative preferences for the phi angle.
研究表明，氨基酸具有各种内在的φ和ψ倾向，这一点可通过实验二级结构倾向与其在拉氏图适当区域的蛋白质数据库中的相对统计分布之间的比较得到证明。然而，这并没有排除这些实验倾向是由于突变位置的二级结构环境导致的上下文效应的结果。为了证明至少存在与上下文效应无关的真实内在φ倾向，我们使用了与φ二面角相关的两种不同的核磁共振参数（J3αHN耦合常数和CαH质子的化学位移），这些参数是在无规卷曲的四肽和五肽以及/或蛋白质中测定的。将这些参数的实验测定值与通过对蛋白质数据库中氨基酸的φ二面角统计分布进行不同的经验和理论方程分析所确定的理论值进行比较，支持了每个氨基酸至少具有不同的φ内在倾向这一观点。考虑蛋白质数据库中的所有构象或仅无规卷曲构象，会产生相似的结果。这些实验数据和理论数据与无规卷曲肽中的氢交换数据之间的合理相关性表明，疏水表面埋藏的最大化以及与溶剂形成氢键可能是造成这些不同的无规卷曲构象偏好的原因。对20种氨基酸在无规卷曲构象中的β-链、α-螺旋和多聚脯氨酸II二面角的内在倾向进行分析表明，氨基酸的侧链主要决定了对φ角的相对偏好。
