Résumé
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.