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

This study was started with a structure predicted using homology modeling method, which later found to be highly consistent with the crystal structure, demonstrating the potentiality of structure prediction and dynamics simulation in revealing molecular details before the availability of high resolution experimental information. Furthermore, the interactions between CoV2-RBD and the ACE2 mutants mimicking rat ACE2 protein were investigated. The results provide valuable information at the atomic level for the reduced binding affinity. The recent report on the SARS-CoV-2 infection to a dog 31 raise the concerns about the COVID-19 transmissions to pet animals. The approach discussed in this study can be applied to analyze the CoV2-RBD interaction with a broader ACE2 variants, including the genetic polymorphism of the ACE2 in human and the ACE2 of other mammalian animals. Preliminary analysis of several ACE2 proteins from mammalian animals using homology modeling and active site prediction methods shows that the binding sites exhibit different features compared to the human ACE2. More thorough and deeper analysis can be carried out using the presented approach.