Computational simulations reveal the binding dynamics between human ACE2 and the receptor binding domain of SARS-CoV-2 spike protein

Cecylia S. Lupala; Xuanxuan Li; Jian Lei; Hong Chen; Jianxun Qi; Haiguang Liu; Xiao-dong Su

The interactions between the RBD and the ACE2 were quantified by physical interaction energies (molecular mechanics energy) and the number of contacting residues. The detailed comparison results suggest that the CoV2-RBD and the SARS-RBD bind to human ACE2 with comparable affinity. The comparison between the SARS-RBD/ACE2 and the CoV2-RBD/ACE2 complexes, with the former forms fewer contacts than the latter (Figure 8 ), yet exhibiting stronger interactions. The decomposition of the E MM to the van der Waals and the electrostatic interactions revealed that the major difference is attributed to the electrostatic interactions. Furthermore, we compared the major contacting residues . CC-BY-NC-ND 4.0 International license author/funder. It is made available under a The copyright holder for this preprint (which was not peer-reviewed) is the . https://doi.org/10.1101/2020.03.24.005561 doi: bioRxiv preprint and found that the SARS-RBD has two charged residues (R426 and D463) and the CoV2-RBD has only one charged residue (K417) at the complex interface. The polar and hydrophobic residues are comparable in the two RBDs. This is consistent with the statistics of hydrogen bonds at the complex interfaces.