Fig. 1.

Molecular docking simulations and frequencies of ACE2 SNPs that either enhance or the affinity with SARS-Cov-2 Spike protein. A) Global Energy Score (GES) (Kcal/mol) of the interaction between wild type ACE2 or ACE2 missense variants and SARS-Cov-2 Spike protein. Molecular docking simulation were carried out by using HDOCK, which is based on two methods: template-based modeling and ab initio free docking. GES here shown are an average of the GES with the two methods. As reference values are shown: the average GES obtained with all simulations (solid line), the confidence interval (dotted line), and the GES obtained with wild type ACE (red line). B–C) Frequencies of ACE2 SNPs that either enhance (I21T, K26R, E37K, T55A) (B), or reduce (I21V, E23K, K26E, T27A, E35K, S43R, Y50F, N51D, N58H, K68E, M82I) (C) the affinity with SARS-Cov-2 Spike protein, based on GES. D–E) Molecular docking simulations of affinity of known RBD mutations of the Spike protein showing that 5 of the 7 RBD mutations increased binding affinity for wild type ACE2 (D), while 5 of the 7 RBD mutations decreased the binding affinity for K26R ACE2 compared to wild type RBD (E).