The role of hydrophobic interactions in folding of $\beta$-sheets

Jiacheng Li; Xiaoliang Ma; Hongchi Zhang; Chengyu Hou; Liping Shi; Shuai Guo; Chenchen Liao; Bing Zheng; Lin Ye; Lin Yang; Xiaodong He

arXiv · 2009.07466

The role of hydrophobic interactions in folding of $\beta$-sheets

Jiacheng Li·Xiaoliang Ma·Hongchi Zhang·Chengyu Hou·Liping Shi·Shuai Guo·Chenchen Liao·Bing Zheng·Lin Ye·Lin Yang·Xiaodong He

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Abstract

Exploring the protein-folding problem has been a long-standing challenge in molecular biology. Protein folding is highly dependent on folding of secondary structures as the way to pave a native folding pathway. Here, we demonstrate that a feature of a large hydrophobic surface area covering most side-chains on one side or the other side of adjacent $\beta$-strands of a $\beta$-sheet is prevail in almost all experimentally determined $\beta$-sheets, indicating that folding of $\beta$-sheets is most likely triggered by multistage hydrophobic interactions among neighbored side-chains of unfolded polypeptides, enable $\beta$-sheets fold reproducibly following explicit physical folding codes in aqueous environments. $\beta$-turns often contain five types of residues characterized with relatively small exposed hydrophobic proportions of their side-chains, that is explained as these residues can block hydrophobic effect among neighbored side-chains in sequence. Temperature dependence of the folding of $\beta$-sheet is thus attributed to temperature dependence of the strength of the hydrophobicity. The hydrophobic-effect-based mechanism responsible for $\beta$-sheets folding is verified by bioinformatics analyses of thousands of results available from experiments. The folding codes in amino acid sequence that dictate formation of a $\beta$-hairpin can be deciphered through evaluating hydrophobic interaction among side-chains of an unfolded polypeptide from a $\beta$-strand-like thermodynamic metastable state.

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Jiacheng Li, Xiaoliang Ma, Hongchi Zhang, Chengyu Hou, Liping Shi, Shuai Guo, Chenchen Liao, Bing Zheng, Lin Ye, Lin Yang, Xiaodong He. 2020-09-16. The role of hydrophobic interactions in folding of $\beta$-sheets. https://arxiv.org/abs/2009.07466

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