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Complex cooperativity in DNA origami revealed via design-dependent defectivity.

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Title: Complex cooperativity in DNA origami revealed via design-dependent defectivity.
Authors: Majikes JM; Theiss Research, La Jolla, CA 92037, United States.; Microsystems and Nanotechnology Division, National Institute of Standards and Technology, Gaithersburg, MD 20899, United States., Hasni A; Biomedical Engineering, Johns Hopkins University, Baltimore, MD 21211,United States., Haridas S; University of Maryland, College Park, MD 20742, United States., Robertson JWF; Microsystems and Nanotechnology Division, National Institute of Standards and Technology, Gaithersburg, MD 20899, United States., Pintar AL; Statistical Engineering Division, National Institute of Standards and Technology, Gaithersburg, MD 92037, United States., Zwolak M; Microsystems and Nanotechnology Division, National Institute of Standards and Technology, Gaithersburg, MD 20899, United States., Liddle JA; Microsystems and Nanotechnology Division, National Institute of Standards and Technology, Gaithersburg, MD 20899, United States.
Source: Nucleic acids research [Nucleic Acids Res] 2026 Feb 05; Vol. 54 (4).
Publication Type: Journal Article
Language: English
Journal Info: Publisher: Oxford University Press Country of Publication: England NLM ID: 0411011 Publication Model: Print Cited Medium: Internet ISSN: 1362-4962 (Electronic) Linking ISSN: 03051048 NLM ISO Abbreviation: Nucleic Acids Res Subsets: MEDLINE
Imprint Name(s): Publication: 1992- : Oxford : Oxford University Press
Original Publication: London, Information Retrieval ltd.
MeSH Terms: DNA Nanostructures*/chemistry , DNA*/chemistry, Nucleic Acid Conformation ; Thermodynamics
Abstract: DNA origami has become a ubiquitous platform because it enables straightforward design of nanostructures that self-assemble with high yield. The interactions between the cooperative effects involved in its assembly are currently not well understood. Fortunately, the nearly infinite number of choices available to the origami designer provides a rich environment in which to explore cooperativity. The DNA domains comprising origami have predictable energetics, and the sources of cooperativity are conceptually straightforward, and the difficulty in predicting assembly comes from their large number of cooperative interactions. We are able to probe cooperativity by using design variations and measuring their effect on assembly yield. We employ an accelerated assembly protocol that increases the sensitivity of structural perfection, or lack thereof, to design variation, and apply this approach to survey a broad set of design features. Using the resulting dataset, we develop metrics to correlate thermal stability, beneficial cooperativity from short folds, and detrimental cooperativity from long folds, with defectivity. Surprisingly, these metrics can be combined to create a single parameter with a clear correlation to yield, which serves as a useful starting place for a predictive understanding of the interplay between cooperativity and design. In doing so, we also identify qualitative trends that provide useful insight into design best practice.
(Published by Oxford University Press 2026.)
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Grant Information: U.S. Department of Commerce
Substance Nomenclature: 9007-49-2 (DNA)
Entry Date(s): Date Created: 20260216 Date Completed: 20260708 Latest Revision: 20260813
Update Code: 20260813
PubMed Central ID: PMC12907558
DOI: 10.1093/nar/gkag052
PMID: 41693566
Database: MEDLINE
Description
ISSN:1362-4962
DOI:10.1093/nar/gkag052