Computational insights into differential interaction of mammalian angiotensin-converting enzyme 2 with the SARS-CoV-2 spike receptor binding domain. (February 2022)

• Record Type: Journal Article
• Authors: Lupala, Cecylia Severin; Kumar, Vikash; Su, Xiao-dong; Wu, Chun; Liu, Haiguang
• Is Part Of: Computers in biology and medicine. Volume 141(2022)
• Publication Date: 2022-02
• Subjects: ACE2 -- Homology modeling -- Molecular dynamics -- RBD -- SARS-CoV-2; Medicine -- Data processing -- Periodicals; Biology -- Data processing -- Periodicals; 610.285
• DOI: 10.1016/j.compbiomed.2021.105017
• Languages: English
• ISSNs: 0010-4825

Abstract

Abstract: The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the causative agent of the COVID-19 pandemic. Angiotensin-converting enzyme 2 (ACE2) has been identified as the host cell receptor that binds to the receptor-binding domain (RBD) of the SARS-COV-2 spike protein and mediates cell entry. Because the ACE2 proteins are widely available in mammals, it is important to investigate the interactions between the RBD and the ACE2 of other mammals. Here we analyzed the sequences of ACE2 proteins from 16 mammals, predicted the structures of ACE2-RBD complexes by homology modeling, and refined the complexes using molecular dynamics simulation. Analyses on sequence, structure, and dynamics synergistically provide valuable insights into the interactions between ACE2 and RBD. The analysis outcomes suggest that the ACE2 of bovine, cat, and panda form strong binding interactions with RBD, while in the cases of rat, least horseshoe bat, horse, pig, mouse, and civet, the ACE2 proteins interact weakly with RBD. Graphical abstract: Image 1 Highlights: Sequence and structure comparison of ACE2 proteins from 16 mammals. Identification of 13 amino acids at the ACE2-RBD complex interface. Characterization of electrostatic potential surfaces of ACE2, at ACE2-RBD interface. Molecular dynamics refinement reveals detailed interactions between ACE2 proteins and RBD. Identifying key residues for viral-host interactions from dynamics simulations.