Density functional theory computation of the binding free energies between various mutations of SARS-CoV-2 RBD and human ACE2: molecular level roots of the contagiousness

The receptor-binding domain (RBD) of SARS-CoV-2 attaches to the human ACE2 to initiate binding of SARS-CoV-2 to human cell and leads to the infection process afterwards. In this study, various mutations of SARS-CoV-2 spike RBD and human ACE2 complexes are investigated via density functional theory (DFT) computations to obtain binding free energies. The DFT computations are performed without fragmenting the interfaces to involve longer-range quantum mechanical interactions for improving accuracy. The vibrational free energies, van der Waals dispersion forces and basis set superposition error corrections are also included in the calculations. The results show that the absolute value of the binding energy of B.1.1.7 mutated spike RBD–ACE2 complex is more than five times higher than that of the original strain. The results of this study are expected to be useful for a deeper understanding of the relation of the binding free energies and the level of contagiousness.