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 results showed that the wild type CoV2-RBD/ACE2 complex is stable in 500 ns simulations, especially in the well-defined binding interface. On the other hand, the mutations on the helix-1 or K353 of the ACE2 can alter the binding, revealing new binding poses with reduced contacts compared to those in the crystal structures. The analysis of the interaction energy showed that the binding is enhanced by adjusting conformations to form . 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 It is made available under a The copyright holder for this preprint (which was not peer-reviewed) is the .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 more favorable interactions as the simulation progressed, consistent with the increased hydrogen bonding patterns. Furthermore, the analysis also showed that SARS-RBD and CoV2-RBD have comparable binding affinities to the ACE2, with the former slightly stronger than the latter in terms of molecular mechanics energies. The dynamic information obtained by this study shall be useful in understanding SARS-CoV-2 host interaction and for designing inhibitors to block CoV2-RBD binding.