Topological constraints in nucleic acid hybridization kinetics
Abstract
A theoretical examination of kinetic mechanisms for forming knots and links in nucleic acid structures suggests that molecules involving base pairs between loops are likely to become topologically trapped in persistent frustrated states through the mechanism of 'helix-driven wrapping'. Augmentation of the state space to include both secondary structure and topology in describing the free energy landscape illustrates the potential for topological effects to influence the kinetics and function of nucleic acid strands. An experimental study of metastable complementary 'kissing hairpins' demonstrates that the topological constraint of zero linking number between the loops effectively prevents conversion to the minimum free energy helical state. Introduction of short catalyst strands that break the topological constraint causes rapid conversion to full duplex.
Additional Information
© The Author 2005. Published by Oxford University Press. The online version of this article has been published under an open access model. Users are entitled to use, reproduce, disseminate, or display the open access version of this article for non-commercial purposes provided that: the original authorship is properly and fully attributed; the Journal and Oxford University Press are attributed as the original place of publication with the correct citation details given; if an article is subsequently reproduced or disseminated not in its entirety but only in part or as a derivative work this must be clearly indicated. For commercial re-use, please contact journals.permissions@oupjournals.org Received April 24, 2005. Revised May 17, 2005. Accepted July 4, 2005. We are grateful to J. Bloom for performing the initial experimental studies on the kissing hairpin system, to G.Seelig for discussions on hybridization catalysts, and to H. Isambert for discussions on the disparity in chain diffusion and helix nucleation time scales. This work was supported by the Charles Lee Powell Foundation (N.A.P.), the Ralph M. Parsons Foundation (N.A.P.), the NSF CAREER program (N.A.P.) and the Caltech Center for Biological Circuit Design (S.V.). Funding to pay the Open Access publication charges for this article was provided by NSF grant CCF-0448835. Conflict of interest statement. None declared. The authors wish it to be known that, in their opinion, the first two authors should be regarded as joint First Authors.Attached Files
Published - BOInar05.pdf
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Additional details
- PMCID
- PMC1180668
- Eprint ID
- 743
- Resolver ID
- CaltechAUTHORS:BOInar05
- Charles Lee Powell Foundation
- Ralph M. Parsons Foundation
- Caltech Center for Biological Circuit Design
- NSF
- CCF-0448835
- Created
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2005-09-23Created from EPrint's datestamp field
- Updated
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2023-06-01Created from EPrint's last_modified field