DOI: 10.1073/pnas.2036378100. Atomistic understanding of kinetic pathways for single base-pair binding and unbinding in DNA

Atomistic understanding of kinetic pathways for single base-pair binding and unbinding in DNA

10.1073/pnas.2036378100

Crossref journal-article

Proceedings of the National Academy of Sciences

Proceedings of the National Academy of Sciences (341)

Abstract

We combine free-energy calculations and molecular dynamics to elucidate a mechanism for DNA base-pair binding and unbinding in atomic detail. Specifically, transition-path sampling is used to overcome computational limitations associated with conventional techniques to harvest many trajectories for the flipping of a terminal cytosine in a 3-bp oligomer in explicit water. Comparison with free-energy projections obtained with umbrella sampling reveals four coordinates that separate true dynamic transition states from stable reactant and product states. Unbinding proceeds via two qualitatively different pathways: one in which the flipping base breaks its intramolecular hydrogen bonds before it unstacks and another in which it ruptures both sets of interactions simultaneously. Both on- and off-pathway intermediates are observed. The relation of the results to coarse-grained models for DNA-based biosensors is discussed.

Bibliography

Hagan, M. F., Dinner, A. R., Chandler, D., & Chakraborty, A. K. (2003). Atomistic understanding of kinetic pathways for single base-pair binding and unbinding in DNA. Proceedings of the National Academy of Sciences, 100(24), 13922â13927.

Authors 4

Michael F. Hagan (first)
Aaron R. Dinner (additional)
David Chandler (additional)
Arup K. Chakraborty (additional)

References 34 Referenced 108

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Dates

Type	When
Created	21 years, 9 months ago (Nov. 25, 2003, 3:59 p.m.)
Deposited	3 years, 4 months ago (April 25, 2022, 9:43 p.m.)
Indexed	1 year ago (Aug. 30, 2024, 6:52 a.m.)
Issued	21 years, 9 months ago (Nov. 14, 2003)
Published	21 years, 9 months ago (Nov. 14, 2003)
Published Online	21 years, 9 months ago (Nov. 14, 2003)
Published Print	21 years, 9 months ago (Nov. 25, 2003)

Funders 0

None

BibTeX

@article{Hagan_2003, title={Atomistic understanding of kinetic pathways for single base-pair binding and unbinding in DNA}, volume={100}, ISSN={1091-6490}, url={http://dx.doi.org/10.1073/pnas.2036378100}, DOI={10.1073/pnas.2036378100}, number={24}, journal={Proceedings of the National Academy of Sciences}, publisher={Proceedings of the National Academy of Sciences}, author={Hagan, Michael F. and Dinner, Aaron R. and Chandler, David and Chakraborty, Arup K.}, year={2003}, month=nov, pages={13922–13927} }

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