Mega-scale experimental analysis of protein folding stability in biology and design.

ABSTRACT: Advances in DNA sequencing and machine learning are providing insights into protein sequences and structures on an enormous scale¹. However, the energetics driving folding are invisible in these structures and remain largely unknown². The hidden thermodynamics of folding can drive disease^3,4, shape protein evolution^5-7 and guide protein engineering^8-10, and new approaches are needed to reveal these thermodynamics for every sequence and structure. Here we present cDNA display proteolysis, a method for measuring thermodynamic folding stability for up to 900,000 protein domains in a one-week experiment. From 1.8 million measurements in total, we curated a set of around 776,000 high-quality folding stabilities covering all single amino aci

SUBMITTER: Tsuboyama K 

PROVIDER: S-EPMC10412457 | biostudies-literature | 2023 Aug

REPOSITORIES: biostudies-literature