DOI: 10.1073/pnas.0606692103. Sampling the multiple folding mechanisms of Trp-cage in explicit solvent

Sampling the multiple folding mechanisms of Trp-cage in explicit solvent

10.1073/pnas.0606692103

Crossref journal-article

Proceedings of the National Academy of Sciences

Proceedings of the National Academy of Sciences (341)

Abstract

We investigate the kinetic pathways of folding and unfolding of the designed miniprotein Trp- cage in explicit solvent. Straightforward molecular dynamics and replica exchange methods both have severe convergence problems, whereas transition path sampling allows us to sample unbiased dynamical pathways between folded and unfolded states and leads to deeper understanding of the mechanisms of (un)folding. In contrast to previous predictions employing an implicit solvent, we find that Trp-cage folds primarily (80% of the paths) via a pathway forming the tertiary contacts and the salt bridge, before helix formation. The remaining 20% of the paths occur in the opposite order, by first forming the helix. The transition states of the rate-limiting steps are solvated native-like structures. Water expulsion is found to be the last step upon folding for each route. Committor analysis suggests that the dynamics of the solvent is not part of the reaction coordinate. Nevertheless, during the transition, specific water molecules are strongly bound and can play a structural role in the folding.

Bibliography

Juraszek, J., & Bolhuis, P. G. (2006). Sampling the multiple folding mechanisms of Trp-cage in explicit solvent. Proceedings of the National Academy of Sciences, 103(43), 15859â15864.

Authors 2

J. Juraszek (first)
P. G. Bolhuis (additional)

References 51 Referenced 224

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Dates

Type	When
Created	18 years, 10 months ago (Oct. 11, 2006, 9:07 p.m.)
Deposited	3 years, 4 months ago (April 12, 2022, 2:40 p.m.)
Indexed	1 month ago (July 28, 2025, 2:48 a.m.)
Issued	18 years, 10 months ago (Oct. 24, 2006)
Published	18 years, 10 months ago (Oct. 24, 2006)
Published Online	18 years, 10 months ago (Oct. 24, 2006)
Published Print	18 years, 10 months ago (Oct. 24, 2006)

Funders 0

None

BibTeX

@article{Juraszek_2006, title={Sampling the multiple folding mechanisms of Trp-cage in explicit solvent}, volume={103}, ISSN={1091-6490}, url={http://dx.doi.org/10.1073/pnas.0606692103}, DOI={10.1073/pnas.0606692103}, number={43}, journal={Proceedings of the National Academy of Sciences}, publisher={Proceedings of the National Academy of Sciences}, author={Juraszek, J. and Bolhuis, P. G.}, year={2006}, month=oct, pages={15859–15864} }

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