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

Although the overall topology is very similar to the wild type complex structure, there are pronounced differences. For the ACE2-mut-h1 system, the CoV2-RBD tilted further away from the ACE12 helix-1 in one simulation (Figure 7a) ; and the CoV2-RBD lost its contact with helix-13 (G326 to N330) in another simulation for the ACE2-K353H (Figure 7c ). In the wild type ACE2, the K353 is a hydrogen donor, and its mutant H353 cannot form the hydrogen bond with the CoV2-RBD as in the wild type CoV2-RBD/ACE2 complex. The number of contacting residue pairs was significantly reduced in the ACE2-K353H mutant system. This is in line with the report that K353 is more critical than the other residues, as 1 1 its hydrophobic neighborhood enables this positively charged residue high selectivity to the RBD 27, 28 .