D614G substitution at the hinge region enhances the stability of trimeric SARS-CoV-2 spike protein.

ABSTRACT: Mutations in the spike protein of SARS-CoV-2 are the major causes for the modulation of ongoing COVID-19 infection. Currently, the D614G substitution in the spike protein has become dominant worldwide. It is associated with higher infectivity than the ancestral (D614)variant. We demonstrate using Gaussian network model-based normal mode analysis that the D614G substitution occurs at the hinge region that facilitates domain-domain motions between receptor binding domain and S2 region of the spike protein. Computer-aided mutagenesis and inter-residue energy calculations reveal that contacts involving D614 are energetically frustrated. However, contacts involving G614 are energetically favourable, implying the substitution strengthens residue contacts that are formed within as well as between

SUBMITTER: Yazhini A 

PROVIDER: S-EPMC8131580 | biostudies-literature | 2021

REPOSITORIES: biostudies-literature