Format

Send to

Choose Destination
See comment in PubMed Commons below
J Mol Biol. 2011 Jan 7;405(1):43-8. doi: 10.1016/j.jmb.2010.10.023. Epub 2010 Oct 23.

Computational design and experimental testing of the fastest-folding β-sheet protein.

Author information

1
D. E. Shaw Research, New York, NY 10036, USA.

Abstract

One of the most important and elusive goals of molecular biology is the formulation of a detailed, atomic-level understanding of the process of protein folding. Fast-folding proteins with low free-energy barriers have proved to be particularly productive objects of investigation in this context, but the design of fast-folding proteins was previously driven largely by experiment. Dramatic advances in the attainable length of molecular dynamics simulations have allowed us to characterize in atomic-level detail the folding mechanism of the fast-folding all-β WW domain FiP35. In the work reported here, we applied the biophysical insights gained from these studies to computationally design an even faster-folding variant of FiP35 containing only naturally occurring amino acids. The increased stability and high folding rate predicted by our simulations were subsequently validated by temperature-jump experiments. The experimentally measured folding time was 4.3 μs at 80 °C-about three times faster than the fastest previously known protein with β-sheet content and in good agreement with our prediction. These results provide a compelling demonstration of the potential utility of very long molecular dynamics simulations in redesigning proteins well beyond their evolved stability and folding speed.

PMID:
20974152
DOI:
10.1016/j.jmb.2010.10.023
[Indexed for MEDLINE]
PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for Elsevier Science
    Loading ...
    Support Center