Mapping the ACE2 binding site on the SARS-CoV-2 spike protein S1: molecular recognition pattern

Coronavirus SARS-CoV-2 enters the host cell via binding with the angiotensin-converting enzyme 2 (ACE2), and here we used computational modelling to study the molecular recognition pattern of this interaction. The fragment of the N-terminal part of the enzyme containing amino acids 19-45 was used as the lead peptide in this study. The structure of this peptide was systematically modified by successive replacement of its amino acids with alanine, serine, glycine, and phenylalanine. Then docking energies were calculated for all these mutant peptides. These docking energies were correlated with physical descriptors, proposed for the modelling of peptide-protein interactions, characterizing hydrophilicity and volume-related properties of amino acid side chains. From these correlations the corresponding specificity factors were obtained for all amino acid positions, and thus the full description of the molecular recognition pattern of the ACE2 alpha 1 domain by the virus S1 protein binding site was obtained.