Stepwise introduction of stabilizing mutations reveals nonlinear additive effects in de novo TIM barrels.

ABSTRACT: Over the past decades, the TIM-barrel fold has served as a model system for the exploration of how changes in protein sequences affect their structural, stability, and functional characteristics, and moreover, how this information can be leveraged to design proteins from the ground up. After numerous attempts to design de novo proteins with this specific fold, sTIM11 was the first validated de novo design of an idealized four-fold symmetric TIM barrel. Subsequent efforts to enhance the stability of this initial design resulted in the development of DeNovoTIMs, a family of de novo TIM barrels with various stabilizing mutations. In this study, we present an investigation into the biophysical and thermodynamic effects upon introducing a varying number of stabilizing mutations per quarter alon

SUBMITTER: Koch JS 

PROVIDER: S-EPMC10880431 | biostudies-literature | 2024 Mar

REPOSITORIES: biostudies-literature