2022/02/22 by Lin Yang, Shuai Guo, Yang, Lin +21
Biochemistry, Genetics and Molecular Biology · Chemistry · #Advanced Proteomics Techniques and Applications #Biomolecules (q-bio.BM) #FOS: Biological sciences #Protein Structure and Dynamics #q-bio.BM
paper · pdf · doi:10.48550/arxiv.2202.10605
arxiv created 2022/02/22 · openalex publication_date 2022/02/22 · arxiv updated 2022/02/23 · openalex created_date 2025/10/10 · openalex updated_date 2026/07/28
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.