Computer-based redesign of a protein folding pathway.

TitleComputer-based redesign of a protein folding pathway.
Publication TypeJournal Article
Year of Publication2001
AuthorsNauli, S., Kuhlman B., & Baker D.
JournalNature structural biology
Date Published2001 Jul
KeywordsAmino Acid Sequence, Bacterial Proteins, Circular Dichroism, Computer Simulation, Guanidine, Kinetics, Models, Molecular, Mutation, Primary Publication, Protein Conformation, Protein Denaturation, Protein Engineering, Protein Folding, Thermodynamics

A fundamental test of our current understanding of protein folding is to rationally redesign protein folding pathways. We use a computer-based design strategy to switch the folding pathway of protein G, which normally involves formation of the second, but not the first, beta-turn at the rate limiting step in folding. Backbone conformations and amino acid sequences that maximize the interaction density in the first beta-hairpin were identified, and two variants containing 11 amino acid replacements were found to be approximately 4 kcal mol-1 more stable than wild type protein G. Kinetic studies show that the redesigned proteins fold approximately 100 x faster than wild type protein and that the first beta-turn is formed and the second disrupted at the rate limiting step in folding.

Alternate JournalNat. Struct. Biol.
nauli01A.pdf1.39 MB