Department of Chemistry, New York University, New York, NY 10003.
Proc Natl Acad Sci U S A. 2014 May 6;111(18):6636-41. doi: 10.1073/pnas.1322833111. Epub 2014 Apr 21.
Helix-coil transition theory connects observable properties of the α-helix to an ensemble of microstates and provides a foundation for analyzing secondary structure formation in proteins. Classical models account for cooperative helix formation in terms of an energetically demanding nucleation event (described by the σ constant) followed by a more facile propagation reaction, with corresponding s constants that are sequence dependent. Extensive studies of folding and unfolding in model peptides have led to the determination of the propagation constants for amino acids. However, the role of individual side chains in helix nucleation has not been separately accessible, so the σ constant is treated as independent of sequence. We describe here a synthetic model that allows the assessment of the role of individual amino acids in helix nucleation. Studies with this model lead to the surprising conclusion that widely accepted scales of helical propensity are not predictive of helix nucleation. Residues known to be helix stabilizers or breakers in propagation have only a tenuous relationship to residues that favor or disfavor helix nucleation.
螺旋-卷曲转变理论将 α-螺旋的可观察性质与微态集联系起来，并为分析蛋白质中二硫键形成提供了基础。经典模型根据能量要求高的成核事件（由σ常数描述）来解释协同螺旋形成，随后是更容易的扩展反应，具有相应的序列依赖性 s 常数。对模型肽的折叠和展开的广泛研究导致了氨基酸扩展常数的确定。然而，单个侧链在螺旋成核中的作用尚无法单独确定，因此σ常数被视为与序列无关。我们在这里描述了一种合成模型，该模型允许评估单个氨基酸在螺旋成核中的作用。对该模型的研究得出了一个令人惊讶的结论，即广泛接受的螺旋倾向尺度并不能预测螺旋成核。在传播中已知是螺旋稳定剂或破坏者的残基与有利于或不利于螺旋成核的残基只有微弱的关系。
