Machine learning reveals the critical interactions for SARS-CoV-2 spike protein binding to ACE2

A novel coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has spread throughout the world. SARS-CoV-2 is less deadly but more transmissible than SARS-CoV, which appeared in late 2002. Both viruses first engage with their host by binding to the same target protein, ACE2. Receptor-binding domain (RBD) is the key that allows the virus to dock to the targeted host protein, ACE2, to gain entry into cells. Herein, we have used molecular dynamics (MD) simulations, machine learning (ML), and free-energy perturbation (FEP) calculations to elucidate the differences in binding by the two viruses.