Global analysis of protein folding using massively parallel design, synthesis, and testing
University of Washington · University of Washington Applied Physics Laboratory · +4 more institutions
Abstract
Proteins fold into unique native structures stabilized by thousands of weak interactions that collectively overcome the entropic cost of folding. Although these forces are "encoded" in the thousands of known protein structures, "decoding" them is challenging because of the complexity of natural proteins that have evolved for function, not stability. We combined computational protein design, next-generation gene synthesis, and a high-throughput protease susceptibility assay to measure folding and stability for more than 15,000 de novo designed miniproteins, 1000 natural proteins, 10,000 point mutants, and 30,000 negative control sequences. This analysis identified more than 2500 stable designed proteins in four…
Citation impact
- FWCI
- 21.30
- Percentile
- 100%
- References
- 91
Authors
12- GJGabriel J. Rocklin
University of Washington
- TMTamuka M. Chidyausiku
University of Washington, University of Washington Applied Physics Laboratory
- IGInna Goreshnik
University of Washington
- AFAlex Ford
University of Washington, University of Washington Applied Physics Laboratory
- SHScott Houliston
University of Toronto, Princess Margaret Cancer Centre, Structural Genomics Consortium
Topics & keywords
- Protein design
- Protein folding
- Folding (DSP implementation)
- Synthetic biology
- Protein engineering
- Sequence space
- Massively parallel
- Computer science