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
Volume8
Issue7
Pagination602-5
Date Published2001 Jul
ISSN1072-8368
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
Abstract

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.
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