Most alanine substitutions exhibited similar or lower total binding affinities to nCOV-2019, however a few mutants had higher binding affinity than the wild type. Mutant Y489A had a total binding energy of −61.78 ± 2.59 kcal/mol which was about 11 kcal/mol lower than wild type binding energy. Mutants G446A, G447A, and T478I also demonstrated higher total binding affinities than nCOV-2019. Other alanine substitutions had similar or lower total binding energy than nCOV-2019. Mutant G502A has the lowest binding affinity among all the mutants with a binding energy of −24.31 ± 2.98 kcal/mol. Mutant systems K417A, L455A, T500A, and N501A are the other mutants with total binding affinities significantly lower than the wild type complex. The electrostatic component of binding contributes the most to the low binding affinities for these mutants. The contribution of RBM residues to binding with ACE2 for nCOV-2019 was mapped to the RBD structure and is shown in Figure 9B.