Structural heterogeneity and precision of implications drawn from cryo-electron microscopy structures: SARS-CoV-2 spike-protein mutations as a test case.

ABSTRACT: Protein structures may be used to draw functional implications at the residue level, but how sensitive are these implications to the exact structure used? Calculation of the effects of SARS-CoV-2 S-protein mutations based on experimental cryo-electron microscopy structures have been abundant during the pandemic. To understand the precision of such estimates, we studied three distinct methods to estimate stability changes for all possible mutations in 23 different S-protein structures (3.69 million ΔΔG values in total) and explored how random and systematic errors can be remedied by structure-averaged mutation group comparisons. We show that computational estimates have low precision, due to method and structure heterogeneity making results for single mutations uninformative. However, struc

SUBMITTER: Mehra R 

PROVIDER: S-EPMC9514682 | biostudies-literature | 2022 Dec

REPOSITORIES: biostudies-literature