Work

Protein folding and unfolding in microseconds to nanoseconds by experiment and simulation

Year: 2000

Type: article

Abstract: The Engrailed Homeodomain protein has the highest refolding and unfolding rate constants directly observed to date. Temperature jump relaxation measurements gave a refolding rate constant of 37,500 s(-1) in water at 25 degrees C, rising to 51,000 s(-1) around 42 degrees C. The unfolding rate constant was 1,100 s(-1) in water at 25 degrees C and 205,000 s(-1) at 63 degrees C. The unfolding half-life is extrapolated to be approximately 7.5 ns at 100 degrees C, which allows real-time molecular dynamics unfolding simulations to be tested on this system at a realistic temperature. Preliminary simulations did indeed conform to unfolding on this time scale. Further, similar transition states were observed in simulations at 100 degrees C and 225 degrees C, suggesting that high-temperature simulations provide results applicable to lower temperatures.

Source: Proceedings of the National Academy of Sciences

DOI: 10.1073/pnas.250473497

Authors: Ugo Mayor, Christopher M. Johnson, Valerie Daggett, Alan R. Fersht

Institutions: University of Washington, University of Cambridge, Medical Research Council

Language: English

Topic: Protein Structure and Dynamics

Subfield: Molecular Biology

Field: Biochemistry, Genetics and Molecular Biology

Domain: Life Sciences

Open Access status: bronze

Funders: National Institutes of Health, University of California, San Francisco, Office of Naval Research, National Institute of General Medical Sciences

Awards: MOLECULAR DYNAMICS SIMULATIONS OF PROTEIN UNFOLDING, G1858193389, Molecular Dynamics Simulations of Protein Unfolding, G8876996369, G9000091166