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Sequence-Dependent Shape and Stiffness of DNA and RNA Double Helices: Hexanucleotide Scale and Beyond

Čmelo, Ivan et al. (2025) Sequence-Dependent Shape and Stiffness of DNA and RNA Double Helices: Hexanucleotide Scale and Beyond. Journal of Chemical Information and Modeling, 65 (17). ISSN 1549-960X

Abstract
The structure and deformability of double-stranded DNA and RNA depend on the sequence of bases, affecting biological processes and nanostructure design, but this dependence is incompletely understood. Here we present mechanical properties of DNA and RNA duplexes inferred from atomic-resolution, explicit-solvent molecular dynamics (MD) simulations of 107 DNA and 107 RNA oligomers containing all hexanucleotide sequences. In addition to the level of rigid bases, minor and major grooves, we probe the length and sequence dependence of global material constants such as persistence lengths, stretching and twisting rigidities. We propose a simple model to predict sequencedependent shape and nonlocal, harmonic stiffness for an arbitrary sequence, validate it on an independent set of MD simulations for DNA and RNA duplexes containing all pentamers, and demonstrate its utility in various applications. The large amount of the simulated data enabled us to study rare events, such as base-pair opening, or flips of the A-RNA sugar pucker into the B domain and the related dynamics of the 2′-OH group. Together, this work provides a comprehensive sequence-specific description of DNA and RNA duplex mechanics, forming a baseline for further research and allowing for a broad range of applications.
Metadata
Item Type:Article (Published)
Refereed:Yes
Subjects:Physical Sciences > Analytical chemistry
Physical Sciences > Chemistry
DCU Faculties and Centres:DCU Faculties and Schools > Faculty of Science and Health
DCU Faculties and Schools > Faculty of Science and Health > School of Chemical Sciences
Publisher:American Chemical Society
Official URL:https://pubs.acs.org/doi/10.1021/acs.jcim.5c00576?...
Copyright Information:Authors
ID Code:31581
Deposited On:29 Sep 2025 11:01 by Gordon Kennedy . Last Modified 29 Sep 2025 11:01
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