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

Based on the analysis of the predicted model, sequence alignment, and literature survey, two other systems containing mutations in the human ACE2 were prepared and subject to MD simulation studies. The mutant construct is based on the fact that Rat ACE2 markedly diminishes interactions with SARS spike protein 12 , and it was proposed that the rat ACE2 likely has reduced binding affinity to the CoV2-RBD 13 . To investigate the roles of critical residues on the ACE2, we created two mutants of the human ACE2 (see Table 1 ): (1) mutant mut_h1, with the ACE2 N-terminal (residue 19-40) mutated to the residues of rat ACE2; and (2) mutant K353H, in which the highly conserved K353 was mutated to histidine (the corresponding amino acid in rat and mouse ACE2 proteins). To focus on the impact of these two binding sites, the rest of the ACE2 were kept to be the same as human ACE2.