Space Layout of Low-entropy Hydration Shells Guides Protein Binding

Lin Yang; Shuai Guo; Chengyu Hou; Chencheng Liao; Jiacheng Li; Liping Shi; Xiaoliang Ma; Shenda Jiang; Bing Zheng; Yi Fang; Lin Ye; Xiaodong He

arXiv · 2202.10605

Space Layout of Low-entropy Hydration Shells Guides Protein Binding

Lin Yang·Shuai Guo·Chengyu Hou·Chencheng Liao·Jiacheng Li·Liping Shi·Xiaoliang Ma·Shenda Jiang·Bing Zheng·Yi Fang·Lin Ye·Xiaodong He

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Abstract

Protein-protein binding enables orderly and lawful biological self-organization, and is therefore considered a miracle of nature. Protein-protein binding is steered by electrostatic forces, hydrogen bonding, van der Waals force, and hydrophobic interactions. Among these physical forces, only the hydrophobic interactions can be considered as long-range intermolecular attractions between proteins in intracellular and extracellular fluid. Low-entropy regions of hydration shells around proteins drive hydrophobic attraction among them that essentially coordinate protein-protein docking in rotational-conformational space of mutual orientations at the guidance stage of the binding. Here, an innovative method was developed for identifying the low-entropy regions of hydration shells of given proteins, and we discovered that the largest low-entropy regions of hydration shells on proteins typically cover the binding sites. According to an analysis of determined protein complex structures, shape matching between the largest low-entropy hydration shell region of a protein and that of its partner at the binding sites is revealed as a regular pattern. Protein-protein binding is thus found to be mainly guided by hydrophobic collapse between the shape-matched low-entropy hydration shells that is verified by bioinformatics analyses of hundreds of structures of protein complexes. A simple algorithm is developed to precisely predict protein binding sites.

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Lin Yang, Shuai Guo, Chengyu Hou, Chencheng Liao, Jiacheng Li, Liping Shi, Xiaoliang Ma, Shenda Jiang, Bing Zheng, Yi Fang, Lin Ye, Xiaodong He. 2022-02-22. Space Layout of Low-entropy Hydration Shells Guides Protein Binding. https://arxiv.org/abs/2202.10605

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