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Nat Struct Biol. 2001 Jul;8(7):602-5.

Computer-based redesign of a protein folding pathway.

Author information

1
[1] Department of Biochemistry and Howard Hughes Medical Institute, University of Washington School of Medicine, Seattle, Washington 98195, USA.

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.

PMID:
11427890
DOI:
10.1038/89638
[Indexed for MEDLINE]

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