Mega-scale experimental analysis of protein folding stability in biology and design
Northwestern University · Japan Science and Technology Agency · +8 more institutions
Abstract
Abstract Advances in DNA sequencing and machine learning are providing insights into protein sequences and structures on an enormous scale 1 . However, the energetics driving folding are invisible in these structures and remain largely unknown 2 . 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…
Citation impact
- FWCI
- 46.36
- Percentile
- 100%
- References
- 91
Authors
9- KTKotaro TsuboyamaCorresponding
Northwestern University, Japan Science and Technology Agency, The University of Tokyo
- JDJustas Dauparas
University of Washington
- JHJonathan H. Chen
Northwestern University, McCormick (United States)
- ÉLÉlodie Laine
Centre National de la Recherche Scientifique, Sorbonne Université, Biologie Computationnelle, Quantitative et Synthétique
- YMYasser Mohseni Behbahani
Centre National de la Recherche Scientifique, Sorbonne Université, Biologie Computationnelle, Quantitative et Synthétique
Topics & keywords
- Protein folding
- Amino acid
- Folding (DSP implementation)
- Proteolysis
- Protein design
- Computational biology
- Protein evolution
- Protein stability
- Life in Land