DOI: 10.1073/pnas.2335541100. Folding a protein in a computer: An atomic description of the folding/unfolding of protein A

Folding a protein in a computer: An atomic description of the folding/unfolding of protein A

10.1073/pnas.2335541100

Crossref journal-article

Proceedings of the National Academy of Sciences

Proceedings of the National Academy of Sciences (341)

Abstract

We study the folding mechanism of a three-helix bundle protein at atomic resolution, including effects of explicit water. Using replica exchange molecular dynamics we perform enough sampling over a wide range of temperatures to obtain the free energy, entropy, and enthalpy surfaces as a function of structural reaction coordinates. Simulations were started from different configurations covering the folded and unfolded states. Because many transitions between all minima at the free energy surface are observed, a quantitative determination of the free energy barriers and the ensemble of configurations associated with them is now possible. The kinetic bottlenecks for folding can be determined from the thermal ensembles of structures on the free energy barriers, provided the kinetically determined transition-state ensembles are similar to those determined from free energy barriers. A mechanism incorporating the interplay among backbone ordering, sidechain packing, and desolvation arises from these calculations. Large Φ values arise not only from native contacts, which mostly form at the transition state, but also from contacts already present in the unfolded state that are partially destroyed at the transition.

Bibliography

GarcÃa, A. E., & Onuchic, J. N. (2003). Folding a protein in a computer: An atomic description of the folding/unfolding of protein A. Proceedings of the National Academy of Sciences, 100(24), 13898â13903.

Authors 2

Angel E. García (first)
José N. Onuchic (additional)

References 45 Referenced 302

Dates

Type	When
Created	21 years, 9 months ago (Nov. 25, 2003, 3:59 p.m.)
Deposited	3 years, 4 months ago (April 13, 2022, 9:27 a.m.)
Indexed	1 month ago (July 30, 2025, 10:52 a.m.)
Issued	21 years, 9 months ago (Nov. 17, 2003)
Published	21 years, 9 months ago (Nov. 17, 2003)
Published Online	21 years, 9 months ago (Nov. 17, 2003)
Published Print	21 years, 9 months ago (Nov. 25, 2003)

Funders 0

None

BibTeX

@article{Garc_a_2003, title={Folding a protein in a computer: An atomic description of the folding/unfolding of protein A}, volume={100}, ISSN={1091-6490}, url={http://dx.doi.org/10.1073/pnas.2335541100}, DOI={10.1073/pnas.2335541100}, number={24}, journal={Proceedings of the National Academy of Sciences}, publisher={Proceedings of the National Academy of Sciences}, author={García, Angel E. and Onuchic, José N.}, year={2003}, month=nov, pages={13898–13903} }

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