Perturbation of ACE2 Structural Ensembles by SARS-CoV-2 Spike Protein Binding.

ABSTRACT: The human ACE2 enzyme serves as a critical first recognition point of coronaviruses, including SARS-CoV-2. In particular, the extracellular domain of ACE2 interacts directly with the S1 tailspike protein of the SARS-CoV-2 virion through a broad protein-protein interface. Although this interaction has been characterized by X-ray crystallography, these structures do not reveal significant differences in the ACE2 structure upon S1 protein binding. In this work, using several all-atom molecular dynamics simulations, we show persistent differences in the ACE2 structure upon binding. These differences are determined with the linear discriminant analysis (LDA) machine learning method and validated using independent training and testing datasets, including long trajectories generated by D. E. Shaw

SUBMITTER: Uyar A 

PROVIDER: S-EPMC8370119 | biostudies-literature | 2021 Sep

REPOSITORIES: biostudies-literature