Figure 16.

Change in binding free energy (ΔΔG = ΔG_WILD-TYPE – ΔG_MUTANT) predicted by computational mutagenesis of the S-RBD_CoV-2 residues Y449 (A), Y453 (B), and T500 (C) for the corresponding ACE2/S-RBD_CoV-2 complexes. In each protein–protein assembly, the wild-type residue is replaced by I, S, T, D/E, K/R, and W. Negative/positive ΔΔG values indicate unfavorable/favorable substitutions for the mutant residue in the relevant position, respectively. The numerical values of ΔΔG, all related energy terms, and all underlying intermolecular/intramolecular interactions are reported in Table S2, Figures S19–S21, and Tables S21–S23. The colored boxes below each bar in the graphs show the qualitative comparison between in silico predicted (upper row) and experimental³⁶ (lower row) destabilizing/stabilizing effects of the corresponding mutation on the ACE2/SARS-CoV-2 S-protein complex. Color legend: light yellow, mildly destabilizing mutations; light red, destabilizing mutations; red, highly destabilizing mutations; gray, neutral mutation; light green, stabilizing mutations; green, highly stabilizing mutations. (D) Main interactions involving the S-RBD_CoV-2 Y453K mutant at the interface with ACE2 as obtained from the relevant equilibrated MD simulations. Colors and other explanations as in Figure 2. Images for all other Y449, Y453, and T500 mutants are shown in Figures S19–S21 (see also Tables S21–23 for details).