2022/04/27 by Lin Yang, Yang, Lin, Shuai Guo +21
Biochemistry, Genetics and Molecular Biology · Chemistry · Environmental Science · Medicine · #Atomic physics #Bacteriophages and microbial interactions #Binding energy #Binding site #Biochemistry #Biology #Biomolecules (q-bio.BM) #Biophysics #Chemical physics #Chemistry #Configuration entropy #Conformational entropy #Crystallography #Entropy (arrow of time) #FOS: Biological sciences #Hydrogen bond #Hydrophobic effect #Lipid Membrane Structure and Behavior #Molecule #Physics #SARS-CoV-2 and COVID-19 Research #Solvation #Solvation shell #Solvent #Thermodynamics #q-bio.BM #van der Waals force
paper · pdf · doi:10.48550/arxiv.2204.12725
27 pages, 14 figures
arxiv created 2022/04/27 · openalex publication_date 2022/04/27 · arxiv updated 2022/04/28 · openalex created_date 2025/10/10 · openalex updated_date 2026/08/08
The infectivity of SARS-CoV-2 depends on the binding affinity of the receptor-binding domain (RBD) of the spike protein with the angiotensin converting enzyme 2 (ACE2) receptor. The calculated RBD-ACE2 binding energies indicate that the difference in transmission efficiency of SARS-CoV-2 variants cannot be fully explained by electrostatic interactions, hydrogen-bond interactions, van der Waals interactions, internal energy, and nonpolar solvation energies. Here, we demonstrate that low-entropy regions of hydration shells around proteins drive hydrophobic attraction between shape-matched low-entropy regions of the hydration shells, which essentially coordinates protein-protein binding in rotational-configurational space of mutual orientations and determines the binding affinity. An innovative method was used to identify the low-entropy regions of the hydration shells of the RBDs of multiple SARS-CoV-2 variants and the ACE2. We observed integral low-entropy regions of hydration shells covering the binding sites of the RBDs and matching in shape to the low-entropy region of hydration shell at the binding site of the ACE2. The RBD-ACE2 binding is thus found to be guided by hydrophobic collapse between the shape-matched low-entropy regions of the hydration shells. A measure of the low-entropy of the hydration shells can be obtained by counting the number of hydrophilic groups expressing hydrophilicity within the binding sites. The low-entropy level of hydration shells at the binding site of a spike protein is found to be an important indicator of the contagiousness of the coronavirus.