Dirks, Robert M. and Lin, Milo and Winfree, Erik and Pierce, Niles A. (2004) Paradigms for computational nucleic acid design. Nucleic Acids Research, 32 (4). pp. 1392-1403. ISSN 0305-1048. PMCID PMC390280. doi:10.1093/nar/gkh291. https://resolver.caltech.edu/CaltechAUTHORS:20110309-104203820
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Abstract
The design of DNA and RNA sequences is critical for many endeavors, from DNA nanotechnology, to PCR‐based applications, to DNA hybridization arrays. Results in the literature rely on a wide variety of design criteria adapted to the particular requirements of each application. Using an extensively studied thermodynamic model, we perform a detailed study of several criteria for designing sequences intended to adopt a target secondary structure. We conclude that superior design methods should explicitly implement both a positive design paradigm (optimize affinity for the target structure) and a negative design paradigm (optimize specificity for the target structure). The commonly used approaches of sequence symmetry minimization and minimum free‐energy satisfaction primarily implement negative design and can be strengthened by introducing a positive design component. Surprisingly, our findings hold for a wide range of secondary structures and are robust to modest perturbation of the thermodynamic parameters used for evaluating sequence quality, suggesting the feasibility and ongoing utility of a unified approach to nucleic acid design as parameter sets are refined further. Finally, we observe that designing for thermodynamic stability does not determine folding kinetics, emphasizing the opportunity for extending design criteria to target kinetic features of the energy landscape.
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Additional Information: | © 2004 Oxford University Press. Received December 14, 2003; Revised and Accepted January 28, 2004. The authors wish to thank D. Baker, A. Condon, S. L. Mayo, N. C. Seeman and R. Schulman for comments on the manuscript, and I. Hofacker for providing the kinetic simulation package Kinfold. The following research support is gratefully acknowledged: NSF graduate research fellowship (R.M.D.), Caltech Axline SURF (M.L.), DARPA and Air Force Research Laboratory under agreement F30602-01020561 (R.M.D., E.W. and N.A.P.) and Ralph M. Parsons Foundation (N.A.P.). | ||||||||||||||
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Issue or Number: | 4 | ||||||||||||||
PubMed Central ID: | PMC390280 | ||||||||||||||
DOI: | 10.1093/nar/gkh291 | ||||||||||||||
Record Number: | CaltechAUTHORS:20110309-104203820 | ||||||||||||||
Persistent URL: | https://resolver.caltech.edu/CaltechAUTHORS:20110309-104203820 | ||||||||||||||
Official Citation: | Robert M. Dirks, Milo Lin, Erik Winfree, and Niles A. Pierce Paradigms for computational nucleic acid design Nucl. Acids Res. (2004) 32(4): 1392-1403 doi:10.1093/nar/gkh291 | ||||||||||||||
Usage Policy: | No commercial reproduction, distribution, display or performance rights in this work are provided. | ||||||||||||||
ID Code: | 22769 | ||||||||||||||
Collection: | CaltechAUTHORS | ||||||||||||||
Deposited By: | Lucinda Acosta | ||||||||||||||
Deposited On: | 10 Mar 2011 18:11 | ||||||||||||||
Last Modified: | 09 Nov 2021 16:07 |
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