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 sequence-dependent 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.

CZ OPENSCREEN National Infrastructure for Chemical Biology Faculty of Chemical Technology University of Chemistry and Technology Prague 166 28 Prague Czech Republic

Department of Informatics and Chemistry University of Chemistry and Technology Prague 166 28 Prague Czech Republic

Department of Physical Chemistry Faculty of Science Palacký University 771 46 Olomouc Czech Republic

Molecular Design Group School of Chemical Sciences Dublin City University D09 V209 Glasnevin Ireland

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J Chem Inf Model. 2025 Oct 1. doi: 10.1021/acs.jcim.5c02218. PubMed

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Holbrook S. R.. Structural principles from large RNAs. Annu. Rev. Biophys. 2008;37:445–464. doi: 10.1146/annurev.biophys.36.040306.132755. PubMed DOI

Drew H. R., Wing R. M., Takano T., Broka C., Tanaka S., Itakura K., Dickerson R. E.. Structure of a B-DNA dodecamer: Conformation and dynamics. Proc. Natl. Acad. Sci. U.S.A. 1981;78:2179–2183. doi: 10.1073/pnas.78.4.2179. PubMed DOI PMC

Olson W. K., Gorin A. A., Lu X.-J., Hock L. M., Zhurkin V. B.. DNA sequence-dependent deformability deduced from protein-DNA crystal complexes. Proc. Natl. Acad. Sci. U.S.A. 1998;95:11163–11168. doi: 10.1073/pnas.95.19.11163. PubMed DOI PMC

Wu Z., Delaglio F., Tjandra N., Zhurkin V. B., Bax A.. Overall structure and sugar dynamics of a DNA dodecamer from homo- and heteronuclear dipolar couplings and 31P chemical shift anisotropy. J. Biomol. NMR. 2003;26:297–315. doi: 10.1023/A:1024047103398. PubMed DOI

Geggier S., Vologodskii A.. Sequence dependence of DNA bending rigidity. Proc. Natl. Acad. Sci. U.S.A. 2010;107:15421–15426. doi: 10.1073/pnas.1004809107. PubMed DOI PMC

Marin-Gonzalez A., Pastrana C. L., Bocanegra R., Martin-Gonzalez A., Vilhena J. G., Perez R., Ibarra B., Aicart-Ramos C., Moreno-Herrero F.. Understanding the paradoxical mechanical response of in-phase A-tracts at different force regimes. Nucleic Acids Res. 2020;48:5024–5036. doi: 10.1093/nar/gkaa225. PubMed DOI PMC

Basu A., Bobrovnikov D. G., Qureshi Z., Kayikcioglu T., Ngo T. T. M., Ranjan A., Eustermann S., Cieza B., Morgan M. T., Hejna M.. et al. Measuring DNA mechanics on the genome scale. Nature. 2021;589:462–467. doi: 10.1038/s41586-020-03052-3. PubMed DOI PMC

Dock-Bregeon A. C., Chevrier B., Podjarny A., Moras D., de Bear J. S., Gough G. R., Gilham P. T., Johnson J. E.. High resolution structure of the RNA duplex [U­(U-A)­6A]­2. Nature. 1988;335:375–378. doi: 10.1038/335375a0. PubMed DOI

Klosterman P. S., Shah S. A., Steitz T. A.. Crystal structures of two plasmid copy control related RNA duplexes: An 18 base pair duplex at 1.20 A resolution and a 19 base pair duplex at 1.55 A resolution. Biochemistry. 1999;38:14784–14792. doi: 10.1021/bi9912793. PubMed DOI

O’Neil-Cabello E., Bryce D. L., Nikonowicz E. P., Bax A.. Measurement of five dipolar couplings from a single 3D NMR multiplet applied to the study of RNA dynamics. J. Am. Chem. Soc. 2004;126:66–67. doi: 10.1021/ja038314k. PubMed DOI

Yesselman J. D., Denny S. K., Bisaria N., Herschlag D., Greenleaf W. J., Das R.. Sequence-dependent RNA helix conformational preferences predictably impact tertiary structure formation. Proc. Natl. Acad. Sci. U.S.A. 2019;116:16847–16855. doi: 10.1073/pnas.1901530116. PubMed DOI PMC

Marin-Gonzalez A., Aicart-Ramos C., Marin-Baquero M., Martin-Gonzalez A., Suomalainen M., Kannan A., Vilhena J. G., Greber U. F., Moreno-Herrero F., Perez R.. Double-stranded RNA bending by AU-tract sequences. Nucleic Acids Res. 2020;48:12917–12928. doi: 10.1093/nar/gkaa1128. PubMed DOI PMC

Rohs R., Jin X., West S. M., Joshi R., Honig B., Mann R. S.. Origins of specificity in protein-DNA recognition. Annu. Rev. Biochem. 2010;79:233–269. doi: 10.1146/annurev-biochem-060408-091030. PubMed DOI PMC

Corley M., Burns M. C., Gene W. Y.. How RNA-binding proteins interact with RNA: Molecules and mechanisms. Mol. Cell. 2020;78:9–29. doi: 10.1016/j.molcel.2020.03.011. PubMed DOI PMC

Kang J. S., Meier J. L., Dervan P. B.. Design of sequence-specific DNA binding molecules for DNA methyltransferase inhibition. J. Am. Chem. Soc. 2014;136:3687–3694. doi: 10.1021/ja500211z. PubMed DOI PMC

Laughlin-Toth S., Carter E. K., Ivanov I., Wilson D.. DNA microstructure influences selective binding of small molecules designed to target mixed-site DNA sequences. Nucleic Acids Res. 2017;45:1297–1306. doi: 10.1093/nar/gkw1232. PubMed DOI PMC

Oh J., Jia T., Xu J., Chong J., Dervan P. B., Wang D.. RNA polymerase II trapped on a molecular treadmill: Structural basis of persistent transcriptional arrest by a minor groove DNA binder. Proc. Natl. Acad. Sci. U.S.A. 2022;119:e2114065119. doi: 10.1073/pnas.2114065119. PubMed DOI PMC

Childs-Disney J., Yang X., Gibaut Q. M. R., Tong Y., Batey R. T., Disney M. D.. Targeting RNA structures with small molecules. Nat. Rev. Drug Discovery. 2022;21:736–762. doi: 10.1038/s41573-022-00521-4. PubMed DOI PMC

Zhou T., Yang L., Yan L., Dror I., Machado A. C. D., Ghane T., Di Felice R., Rohs R.. DNAshape: a method for the high-throughput prediction of DNA structural features on a genomic scale. Nucleic Acids Res. 2013;41:W56–W62. doi: 10.1093/nar/gkt437. PubMed DOI PMC

Li J., Sagendorf J. M., Chiu T.-P., Pasi M., Perez A., Rohs R.. Expanding the repertoire of DNA shape features of genome-scale studies of transcription factor binding. Nucleic Acids Res. 2017;45:12877–12887. doi: 10.1093/nar/gkx1145. PubMed DOI PMC

Chiu T.-P., Xin B., Markarian N., Wang Y., Rohs R.. TFBSshape: an expanded motif database for DNA shape features of transcription factor binding sites. Nucleic Acids Res. 2020;48:D246–D255. doi: 10.1093/nar/gkz970. PubMed DOI PMC

Li J., Chiu T.-P., Rohs R.. Predicting DNA structure using a deep learning method. Nat. Commun. 2024;15:1243. doi: 10.1038/s41467-024-45191-5. PubMed DOI PMC

Samee M. A. H., Bruneau B. G., Pollard K. S.. A de novo shape motif discovery algorithm reveals preferences of transcription factors for DNA shape beyond sequence motifs. Cell Syst. 2019;8:27–42. doi: 10.1016/j.cels.2018.12.001. PubMed DOI PMC

Barissi S., Sala A., Wieczor M., Battistini F., Orozco M.. DNAffinity: a machine-learning approach to predict DNA binding affinities of transcription factors. Nucleic Acids Res. 2022;50:9105–9114. doi: 10.1093/nar/gkac708. PubMed DOI PMC

Duran E., Djebali S., Gonzalez S., Flores O., Mercader J. M., Guigo R., Torrents D., Soler-Lopez M., Orozco M.. Unravelling the hidden DNA structural/physical code provides novel insights on promoter location. Nucleic Acids Res. 2013;41:7220–7230. doi: 10.1093/nar/gkt511. PubMed DOI PMC

Mishra A., Dhanda S., Siwach P., Aggarwal S., Jayaram B.. A novel method SEProm for prokaryotic promoter prediction based on DNA structure and energetics. Bioinformatics. 2020;36:2375–2384. doi: 10.1093/bioinformatics/btz941. PubMed DOI

Kim S. H., Ganji M., Kim E., van der Torre J., Abbondanzieri E., Dekker C.. DNA sequence encodes the position of DNA supercoils. eLife. 2018;7:e36557. doi: 10.7554/elife.36557. PubMed DOI PMC

Kaplan N., Moore I. K., Fondufe-Mittendorf Y., Gossett A. J., Tillo D., Field Y., LeProust E. M., Hughes T. R., Lieb J. D., Widom J.. et al. The DNA-encoded nucleosome organization of a eukaryotic genome. Nature. 2009;458:362–366. doi: 10.1038/nature07667. PubMed DOI PMC

Onufriev A. V., Schiessel H.. The nucleosome: from structure to function through physics. Curr. Opin. Struct. Biol. 2019;56:119–130. doi: 10.1016/j.sbi.2018.11.003. PubMed DOI

Neipel J., Brandani G., Schiessel H.. Translational nucleosome positioning: A computational study. Phys. Rev. E. 2020;101:022405. doi: 10.1103/PhysRevE.101.022405. PubMed DOI

Li S., Yunhui P., Landsman D., Panchenko A. R.. DNA methylation cues in nucleosome geometry, stability and unwrapping. Nucleic Acids Res. 2022;50:1864–1874. doi: 10.1093/nar/gkac097. PubMed DOI PMC

Farr S. E., Woods E. J., Joseph J. A., Garaizar A., Collepardo-Guevara R.. Nucleosome plasticity is a critical element of chromatin liquid-liquid phase separation and multivalent nucleosome interactions. Nat. Commun. 2021;12:2883. doi: 10.1038/s41467-021-23090-3. PubMed DOI PMC

Sponer J., Bussi G., Krepl M., Banas P., Bottaro S., Cunha R. A., Gil-Ley A., Pinamonti G., Poblete S., Jurecka P.. et al. RNA structural dynamics as captured by molecular simulations: A comprehensive overview. Chem. Rev. 2018;118:4177–4338. doi: 10.1021/acs.chemrev.7b00427. PubMed DOI PMC

Xue L., Lenz S., Zimmermann-Kogadeeva M., Tegunov D., Cramer P., Bork P., Rappsilber J., Mahamid J.. Visualizing translation dynamics at atomic detail inside a bacterial cell. Nature. 2022;610:205–211. doi: 10.1038/s41586-022-05255-2. PubMed DOI PMC

Seeman N. C., Sleiman H. F.. DNA nanotechnology. Nat. Rev. Mater. 2017;3:17068. doi: 10.1038/natrevmats.2017.68. DOI

Guo P.. The emerging field of RNA nanotechnology. Nat. Nanotechnol. 2010;5:833–842. doi: 10.1038/nnano.2010.231. PubMed DOI PMC

Paloncyova M., Pykal M., Kuhrova P., Banaš P., Sponer J., Otyepka M.. Computer aided development of nucleic acid applications in nanotechnologies. Small. 2022;18:2204408. doi: 10.1002/smll.202204408. PubMed DOI

Haggenmueller S., Matthies M., Sample M., Sulc P.. How we simulate DNA origami. Small Methods. 2025;9:2401526. doi: 10.1002/smtd.202401526. PubMed DOI PMC

Lankas F.. DNA sequence-dependent deformability - insights from computer simulations. Biopolymers. 2004;73:327–339. doi: 10.1002/bip.10542. PubMed DOI

Aggarwal A., Nasrak S., Sahoo A. K., Mogurampelly S., Garai A., Maiti P. K.. What do we know about DNA mechanics so far? Curr. Opin. Struct. Biol. 2020;64:42–50. doi: 10.1016/j.sbi.2020.05.010. PubMed DOI

da Rosa G., Grille L., Calzada V., Ahmad K., Arcon J. P., Battistini F., Bayarri G., Bishop T. C., Carloni P., Cheatham III T. E.. et al. Sequence-dependent structural properties of B-DNA: what have we learned in 40 years? Biophys. Rev. 2021;13:995–1005. doi: 10.1007/s12551-021-00893-8. PubMed DOI PMC

Marin-Gonzalez A., Vilhena J. G., Perez R., Moreno-Herrero F.. A molecular view of DNA flexibility. Q. Rev. Biophys. 2021;54:e8. doi: 10.1017/s0033583521000068. PubMed DOI

Basu A., Bobrovnikov D. G., Ha T.. DNA mechanics and its biological impact. J. Mol. Biol. 2021;433:166861. doi: 10.1016/j.jmb.2021.166861. PubMed DOI

Dohnalova H., Lankas F.. Deciphering the mechanical properties of B-DNA duplex. Wiley Interdiscip. Rev.: Comput. Mol. Sci. 2022;12:e1575. doi: 10.1002/wcms.1575. DOI

Cruz-Leon, S. ; Assenza, S. ; Poblete, S. ; Guzman, H. V. . In Physical virology; Comas-Garcia, M. , Rosales-Mendoza, S. , Eds.; Springer: Cham, 2023.

Diekmann S.. Definitions and nomenclature of nucleic acid structure parameters. J. Mol. Biol. 1989;205:787–791. doi: 10.1016/0022-2836(89)90324-0. PubMed DOI

Olson W. K., Bansal M., Burley S. K., Dickerson R. E., Gerstein M., Harvey S. C., Heinemann U., Lu X.-J., Neidle S., Shakked Z.. et al. A standard reference frame for the description of nucleic acid base-pair geometry. J. Mol. Biol. 2001;313:229–237. doi: 10.1006/jmbi.2001.4987. PubMed DOI

Lu X.-J., Olson W. K.. 3DNA: a software package for the analysis, rebuilding and visualization of three-dimensional nucleic acid structures. Nucleic Acids Res. 2003;31:5108–5121. doi: 10.1093/nar/gkg680. PubMed DOI PMC

Lavery R., Moakher M., Maddocks J. H., Petkeviciute D., Zakrzewska K.. Conformational analysis of nucleic acids revisited: Curves+ Nucleic Acids Res. 2009;37:5917–5929. doi: 10.1093/nar/gkp608. PubMed DOI PMC

Lankas F., Sponer J., Langowski J., Cheatham III T. E.. DNA basepair step deformability inferred from molecular dynamics simulations. Biophys. J. 2003;85:2872–2883. doi: 10.1016/S0006-3495(03)74710-9. PubMed DOI PMC

Lankas F., Sponer J., Langowski J., Cheatham III T. E.. DNA deformability at the base pair level. J. Am. Chem. Soc. 2004;126:4124–4125. doi: 10.1021/ja0390449. PubMed DOI

Beveridge D. L., Barreiro G., Byun K. S., Case D. A., Cheatham III T. E., Dixit S. B., Giudice E., Lankas F., Lavery R., Maddocks J. H.. et al. Molecular dynamics simulations of the 136 unique tetranucleotide sequences of DNA oligonucleotides. I. Research design and results on d­(CpG) steps. Biophys. J. 2004;87:3799–3813. doi: 10.1529/biophysj.104.045252. PubMed DOI PMC

Pasi M., Maddocks J. H., Beveridge D. L., Bishop T. C., Case D. A., Cheatham III T. E., Dans P. D., Jayaram B., Lankas F., Laughton C. A.. et al. μABC: a systematic microsecond molecular dynamics study of tetranucleotide sequence effects in B-DNA. Nucleic Acids Res. 2014;42:12272–12283. doi: 10.1093/nar/gku855. PubMed DOI PMC

Dans P. D., Balaceanu A., Pasi M., Patelli A. S., Petkeviciute D., Walther J., Hospital A., Bayarri G., Lavery R., Maddocks J. H.. et al. The static and dynamic structural heterogeneities of B-DNA: extending Calladine-Dickerson rules. Nucleic Acids Res. 2019;47:11090–11102. doi: 10.1093/nar/gkz905. PubMed DOI PMC

Young R. T., Czapla L., Wefers Z. O., Cohen B. M., Olson W. K.. Revisiting DNA sequence-dependent deformability in high-resolution structures: effects of flanking base pairs on dinucleotide morphology and global chain configuration. Life. 2022;12:759. doi: 10.3390/life12050759. PubMed DOI PMC

Zgarbova M., Jurecka P., Lankas F., Cheatham III T. E., Sponer J., Otyepka M.. Influence of BII backbone substates on DNA twist: A unified view and comparison of simulation and experiment for all 136 distinct tetranucleotide sequences. J. Chem. Inf. Model. 2017;57:275–287. doi: 10.1021/acs.jcim.6b00621. PubMed DOI

Walther J., Dans P. D., Balaceanu A., Hospital A., Bayarri G., Orozco M.. A multi-modal coarse grained model of DNA flexibility mappable to the atomistic level. Nucleic Acids Res. 2020;48:e29. doi: 10.1093/nar/gkaa015. PubMed DOI PMC

Eslami-Mossallam B., Ejtehadi M. R.. Contribution of nonlocal interactions to DNA elasticity. J. Chem. Phys. 2011;134:125106. doi: 10.1063/1.3567185. PubMed DOI

Skoruppa E., Voorspoels A., Vreede J., Carlon E.. Length-scale-dependent elasticity in DNA from coarse-grained and all-atom models. Phys. Rev. E. 2021;103:042408. doi: 10.1103/PhysRevE.103.042408. PubMed DOI

Segers M., Voorspoels A., Sakaue T., Carlon E.. Mechanical properties of nucleic acids and the non-local twistable wormlike chain model. J. Chem. Phys. 2022;156:234105. doi: 10.1063/5.0089166. PubMed DOI

Gutiérrez Fosado Y. A., Landuzzi F., Sakaue T.. Coarse Graining DNA: Symmetry, Nonlocal Elasticity, and Persistence Length. Phys. Rev. Lett. 2023;130:058402. doi: 10.1103/physrevlett.130.058402. PubMed DOI

Laeremans W., Segers M., Voorspoels A., Carlon E., Hooyberghs J.. Insights into elastic properties of coarse-grained DNA models: q-stiffness of cgDNA vs cgDNA+ J. Chem. Phys. 2024;160:144105. doi: 10.1063/5.0197053. PubMed DOI

Lankas F., Gonzalez O., Heffler L. M., Stoll G., Moakher M., Maddocks J. H.. On the parameterization of rigid base and basepair models of DNA from molecular dynamics simulations. Phys. Chem. Chem. Phys. 2009;11:10565–10588. doi: 10.1039/b919565n. PubMed DOI

Gonzalez O., Petkeviciute D., Maddocks J. H.. A sequence-dependent rigid-base model of DNA. J. Chem. Phys. 2013;138:055102. doi: 10.1063/1.4789411. PubMed DOI

Petkeviciute D., Pasi M., Gonzalez O., Maddocks J. H.. cgDNA: a software package for the prediction of sequence-dependent coarse-grain free energies of B-form DNA. Nucleic Acids Res. 2014;42:e153. doi: 10.1093/nar/gku825. PubMed DOI PMC

Sharma R., Patelli A. S., De Bruin L., Maddocks J. H.. cgNA+web: A visual interface to the cgna+ sequence-dependent statistical mechanics model of double-stranded nucleic acids. J. Mol. Biol. 2023;435:167978. doi: 10.1016/j.jmb.2023.167978. PubMed DOI

Liebl K., Zacharias M.. Accurate modeling of DNA conformational flexibility by a multivariate Ising model. Proc. Natl. Acad. Sci. U.S.A. 2021;118:e2021263118. doi: 10.1073/pnas.2021263118. PubMed DOI PMC

Lopez-Guell K., Battistini F., Orozco M.. Correlated motions in DNA: Beyond base-pair step models of DNA flexibility. Nucleic Acids Res. 2023;51:2633–2640. doi: 10.1093/nar/gkad136. PubMed DOI PMC

Rohs R., Sklenar H., Shakked Z.. Structural and energetic origins of sequence-specific DNA bending: Monte Carlo simulations of papillomavirus E2-DNA binding sites. Struct. 2005;13:1499–1509. doi: 10.1016/j.str.2005.07.005. PubMed DOI

Sklenar H., Wustner D., Rohs R.. Using internal and collective variables in Monte Carlo simulations of nucleic acids structures: Chain breakage/closure algorithm and associated Jacobians. J. Comput. Chem. 2006;27:309–315. doi: 10.1002/jcc.20345. PubMed DOI

Slattery M., Riley T., Liu P., Abe N., Gomez-Alcala P., Dror I., Zhou T., Rohs R., Honig B., Bussemaker H. J.. et al. Cofactor binding evokes latent differences in DNA binding specificity between Hox proteins. Cell. 2011;147:1270–1282. doi: 10.1016/j.cell.2011.10.053. PubMed DOI PMC

Bonnell V. A., Zhang Y., Brown A. S., Horton J., Josling G. A., Chiu T.-P., Rohs R., Mahony S., Gordan R., Llinas M.. DNA sequence and chromatin differentiate sequence-specific transcription factor binding in the human malaria parasite Plasmodium falciparum . Nucleic Acids Res. 2024;52:10161–10179. doi: 10.1093/nar/gkae585. PubMed DOI PMC

Ghoshdastidar D., Bansal M.. Flexibility of flanking DNA is a key determinant of transcription factor affinity for the core motif. Biophys. J. 2022;121:3987–4000. doi: 10.1016/j.bpj.2022.08.015. PubMed DOI PMC

Chiu T. K., Li J., Jiang Y., Rohs R.. It is in the flanks: Conformational flexibility of transcription factor binding sites. Biophys. J. 2022;121:3765–3767. doi: 10.1016/j.bpj.2022.09.020. PubMed DOI PMC

Chen N., Yu J., Liu Z., Meng L., Li X., Wong K.-C.. Discovering DNA shape motifs with multiple DNA shape features: generalization, methods, and validation. Nucleic Acids Res. 2024;52:4137–4150. doi: 10.1093/nar/gkae210. PubMed DOI PMC

Gaillard T., Case D. A.. Evaluation of DNA force fields in implicit solvation. J. Chem. Theory Comput. 2011;7:3181–3198. doi: 10.1021/ct200384r. PubMed DOI PMC

Orenstein Y., Shamir R.. Design of shortest double-stranded DNA sequences covering all k-mers with applications to protein-binding microarrays and synthetic enhancers. Bioinformatics. 2013;29:i71–i79. doi: 10.1093/bioinformatics/btt230. PubMed DOI PMC

Zgarbova M., Otyepka M., Sponer J., Lankas F., Jurecka P.. Base pair fraying in molecular dynamics simulations of DNA and RNA. J. Chem. Theory Comput. 2014;10:3177–3189. doi: 10.1021/ct500120v. PubMed DOI

Dohnalova H., Matouskova E., Lankas F.. Temperature-dependent elasticity of DNA, RNA and hybrid double helices. Biophys. J. 2024;123:572–583. doi: 10.1016/j.bpj.2024.01.032. PubMed DOI PMC

Zgarbova M., Sponer J., Otyepka M., Cheatham III T. E., Galindo-Murillo R., Jurecka P.. Refinement of the sugar-phosphate backbone torsion beta for Amber force fields improves the description of Z- and B-DNA. J. Chem. Theory Comput. 2015;11:5723–5736. doi: 10.1021/acs.jctc.5b00716. PubMed DOI

Ivani I., Dans P. D., Noy A., Perez A., Faustino I., Hospital A., Walther J., Andrio P., Goni R., Balaceanu A.. et al. Parmbsc1: a refined force field for DNA simulations. Nat. Methods. 2016;13:55–58. doi: 10.1038/nmeth.3658. PubMed DOI PMC

Liebl K., Zacharias M.. Tumuc1: A new accurate DNA force field consistent with high-level quantum chemistry. J. Chem. Theory Comput. 2021;17:7096–7105. doi: 10.1021/acs.jctc.1c00682. PubMed DOI

Zgarbova M., Sponer J., Jurecka P.. Z-DNA as a touchstone for additive empirical force fields and a refinement of the alpha/gamma DNA torsions for Amber. J. Chem. Theory Comput. 2021;17:6292–6301. doi: 10.1021/acs.jctc.1c00697. PubMed DOI

Zgarbova M., Sponer J., Jurecka P.. Refinement of the sugar puckering torsion potential in the Amber DNA force field. J. Chem. Theory Comput. 2025;21:833–846. doi: 10.1021/acs.jctc.4c01100. PubMed DOI PMC

Galindo-Murillo R., Robertson J. C., Zgarbova M., Sponer J., Otyepka M., Jurecka P., Cheatham III T. E.. Assessing the current state of Amber force field modifications for DNA. J. Chem. Theory Comput. 2016;12:4114–4127. doi: 10.1021/acs.jctc.6b00186. PubMed DOI PMC

Dans P. D., Ivani I., Hospital A., Portella G., Gonzalez C., Orozco M.. How accurate are accurate force-fields for B-DNA? Nucleic Acids Res. 2017;45:4217–4230. doi: 10.1093/nar/gkw1355. PubMed DOI PMC

Love O., Galindo-Murillo R., Zgarbova M., Sponer J., Jurecka P., Cheatham III T. E.. Assessing the current state of Amber force field modifications for DNA - 2023 edition. J. Chem. Theory Comput. 2023;19:4299–4307. doi: 10.1021/acs.jctc.3c00233. PubMed DOI PMC

Zgarbova M., Otyepka M., Sponer J., Mladek A., Banas P., Cheatham III T. E., Jurecka P.. Refinement of the Cornell et al. nucleic acids force field based on reference quantum chemical calculations of glycosidic torsion profiles. J. Chem. Theory Comput. 2011;7:2886–2902. doi: 10.1021/ct200162x. PubMed DOI PMC

Banas P., Hollas D., Zgarbova M., Jurecka P., Orozco M., Cheatham III T. E., Sponer J., Otyepka M.. Performance of molecular mechanics force fields for RNA simulations: stability of UUCG and GNRA hairpins. J. Chem. Theory Comput. 2010;6:3836–3849. doi: 10.1021/ct100481h. PubMed DOI PMC

Kuhrova P., Mlynsky V., Otyepka M., Sponer J., Banas P.. Sensitivity of the RNA structure to ion conditions as probed by molecular dynamics simulations of common canonical RNA duplexes. J. Chem. Inf. Model. 2023;63:2133–2146. doi: 10.1021/acs.jcim.2c01438. PubMed DOI PMC

Dang L. X.. Mechanism and thermodynamics of ion selectivity in aqueous solutions of 18-crown-6 ether: a molecular dynamics study. J. Am. Chem. Soc. 1995;117:6954–6960. doi: 10.1021/ja00131a018. DOI

Saenger, W. Principles of Nucleic Acid Structure; Springer Verlag: New York, 1984.

Hopkins C. W., Le Grand S., Walker R. C., Roitberg A.. Long-time-step molecular dynamics through hydrogen mass repartitioning. J. Chem. Theory Comput. 2015;11:1864–1874. doi: 10.1021/ct5010406. PubMed DOI

Roe D. R., Cheatham T. E. III. Parallelization of CPPTRAJ enables large scale analysis of molecular dynamics trajectory data. J. Comput. Chem. 2018;39:2110–2117. doi: 10.1002/jcc.25382. PubMed DOI PMC

El Hassan M. A., Calladine C. R.. Two distinct modes of protein-induced bending in DNA. J. Mol. Biol. 1998;282:331–343. doi: 10.1006/jmbi.1998.1994. PubMed DOI

Kamien R. D., Lubensky T. C., Nelson P., O’Hern C. S.. Direct determination of DNA twist-stretch coupling. Europhys. Lett. 1997;38:237–242. doi: 10.1209/epl/i1997-00231-y. DOI

Nelson P.. New measurements of DNA twist elasticity. Biophys. J. 1998;74:2501–2503. doi: 10.1016/S0006-3495(98)77958-5. PubMed DOI PMC

Lankas F., Sponer J., Hobza P., Langowski J.. Sequence-dependent elastic properties of DNA. J. Mol. Biol. 2000;299:695–709. doi: 10.1006/jmbi.2000.3781. PubMed DOI

Wang J. C.. Helical repeat of DNA in solution. Proc. Natl. Acad. Sci. U.S.A. 1979;76:200–203. doi: 10.1073/pnas.76.1.200. PubMed DOI PMC

Rhodes D., Klug A.. Helical periodicity of DNA determined by enzyme digestion. Nature. 1980;286:573–578. doi: 10.1038/286573a0. PubMed DOI

Zettl T., Mathew R. S., Seifert S., Doniach S., Harbury P. A., Lipfert J.. Absolute Intramolecular Distance Measurements with Angstrom-Resolution Using Anomalous Small-Angle X-ray Scattering. Nano Lett. 2016;16:5353–5357. doi: 10.1021/acs.nanolett.6b01160. PubMed DOI

Bhattacharyya A., Murchie A. I. H., Lilley D. M. J.. RNA bulges and the helical periodicity of double-stranded RNA. Nature. 1990;343:484–487. doi: 10.1038/343484a0. PubMed DOI

Abels J. A., Moreno-Herrero F., van der Heijden T., Dekker C., Dekker N. H.. Single-molecule measurements of the persistence length of double-stranded RNA. Biophys. J. 2005;88:2737–2744. doi: 10.1529/biophysj.104.052811. PubMed DOI PMC

Sharma, R. École Polytechnique Fédérale de Lausanne: Lausanne, 2023.

Gonzalez O., Pasi M., Petkeviciute D., Glowacki J., Maddocks J. H.. Absolute versus relative entropy parameter estimation in a coarse-grain model of DNA. Multiscale Model. Simul. 2017;15:1073–1107. doi: 10.1137/16M1086091. DOI

Glowacki, J. Computer Vision Laboratory. Doctoral Thesis, École Polytechnique Fédérale de Lausanne, Lausanne, 2016.

Moakher M.. On the averaging of symmetric positive-definite tensors. J. Elasticity. 2006;82:273–296. doi: 10.1007/s10659-005-9035-z. DOI

Liebl K., Drsata T., Lankas F., Lipfert J., Zacharias M.. Explaining the striking difference in twist-stretch coupling between DNA and RNA: A comparative molecular dynamics analysis. Nucleic Acids Res. 2015;43:10143–10156. doi: 10.1093/nar/gkv1028. PubMed DOI PMC

Mitchell J. S., Glowacki J., Grandchamp A. E., Manning R. S., Maddocks J. H.. Sequence-dependent persistence lengths of DNA. J. Chem. Theory Comput. 2017;13:1539–1555. doi: 10.1021/acs.jctc.6b00904. PubMed DOI

Fathizadeh A., Eslami-Mossallam B., Ejtehadi M. R.. Definition of the persistence length in the coarse-grained models of DNA elasticity. Phys. Rev. E. 2012;86:051907. doi: 10.1103/PhysRevE.86.051907. PubMed DOI

Kriegel F., Ermann N., Lipfert J.. Probing the mechanical properties, conformational changes, and interactions of nucleic acids with magnetic tweezers. J. Struct. Biol. 2017;197:26–36. doi: 10.1016/j.jsb.2016.06.022. PubMed DOI

Brackley C. A., Morozov A. N., Marenduzzo D.. Models for twistable elastic polymers in Brownian dynamics, and their implementation for LAMMPS. J. Chem. Phys. 2014;140:135103. doi: 10.1063/1.4870088. PubMed DOI

Nomidis S. K., Kriegel F., Vanderlinden W., Lipfert J., Carlon E.. Twist-bend coupling and the torsional response of double-stranded DNA. Phys. Rev. Lett. 2017;118:217801. doi: 10.1103/PhysRevLett.118.217801. PubMed DOI

Drsata T., Perez A., Orozco M., Morozov A. V., Sponer J., Lankas F.. Structure, stiffness and substates of the Dickerson-Drew dodecamer. J. Chem. Theory Comput. 2013;9:707–721. doi: 10.1021/ct300671y. PubMed DOI PMC

Stelzl L. S., Erlenbach N., Heinz M., Prisner T. F., Hummer G.. Resolving the conformational dynamics of DNA with Angstrom resolution by pulsed electron-electron double resonance and molecular dynamics. J. Am. Chem. Soc. 2017;139:11674–11677. doi: 10.1021/jacs.7b05363. PubMed DOI

Sponer J., Florian J., Ng H.-L., Sponer J. E., Spackova N.. Local conformational variations observed in B-DNA crystals do not improve base stacking: computational analysis of base stacking in a d­(CATGGGCCCATG) B-A intermediate crystal structure. Nucleic Acids Res. 2000;28:4893–4902. doi: 10.1093/nar/28.24.4893. PubMed DOI PMC

Sponer J., Jurecka P., Hobza P.. Accurate interaction energies of hydrogen-bonded nucleic acid base pairs. J. Am. Chem. Soc. 2004;126:10142–10151. doi: 10.1021/ja048436s. PubMed DOI

Sponer J., Jurecka P., Marchan I., Luque F. J., Orozco M., Hobza P.. Nature of base stacking: Reference quantum-chemical stacking energies in ten unique B-DNA base-pair steps. Chem.Eur. J. 2006;12:2854–2865. doi: 10.1002/chem.200501239. PubMed DOI

Svozil D., Hobza P., Sponer J.. Comparison of intrinsic stacking energies of ten unique dinucleotide steps in A-RNA and B-DNA duplexes. Can we determine correct order of stability by quantum-chemical calculations? J. Phys. Chem. B. 2010;114:1191–1203. doi: 10.1021/jp910788e. PubMed DOI

Peters J. P., Maher L. J. III. DNA curvature and flexibility in vitro and in vivo . Q. Rev. Biophys. 2010;43:23–63. doi: 10.1017/S0033583510000077. PubMed DOI PMC

Peters J. P., Mogil L. S., McCauley M. J., Williams M. C., Maher L. J. III. Mechanical properties of base-modified DNA are not strictly determined by base stacking or electrostatic interactions. Biophys. J. 2014;107:448–459. doi: 10.1016/j.bpj.2014.04.066. PubMed DOI PMC

Baumann C. G., Smith S. B., Bloomfield V. A., Bustamante C.. Ionic effects on the elasticity of single DNA molecules. Proc. Natl. Acad. Sci. U.S.A. 1997;94:6185–6190. doi: 10.1073/pnas.94.12.6185. PubMed DOI PMC

Herrero-Galan E., Fuentes-Perez M. E., Carrasco C., Valpuesta J. M., Carrascosa J. L., Moreno-Herrero F., Arias-Gonzalez J. R.. Mechanical identities of RNA and DNA double helices unveiled at the single-molecule level. J. Am. Chem. Soc. 2013;135:122–131. doi: 10.1021/ja3054755. PubMed DOI

Kriegel F., Ermann N., Forbes R., Dulin D., Dekker N. H., Lipfert J.. Probing the salt dependence of the torsional stiffness of DNA by multiplexed magnetic torque tweezers. Nucleic Acids Res. 2017;45:5920–5929. doi: 10.1093/nar/gkx280. PubMed DOI PMC

Strauss J. K., Maher L. J. III. DNA bending by asymmetric phosphate neutralization. Science. 1994;266:1829–1834. doi: 10.1126/science.7997878. PubMed DOI

Spiriti J., Kamberaj H., de Graff A. M. R., Thorpe M. F., van der Vaart A.. DNA bending through large angles is aided by ionic screening. J. Chem. Theory Comput. 2012;8:2145–2156. doi: 10.1021/ct300177r. PubMed DOI

Dong H.-L., Zhang C., Dai L., Zhang Y., Zhang X.-H., Tan Z.-J.. The origin of different bending stiffness between double-stranded RNA and DNA revealed by magnetic tweezers and simulations. Nucleic Acids Res. 2024;52:2519–2529. doi: 10.1093/nar/gkae063. PubMed DOI PMC

Everaers R., Bundschuh R., Kremer K.. Fluctuations and stiffness of double-stranded polymers: Railway-rack model. Europhys. Lett. 1995;29:263–268. doi: 10.1209/0295-5075/29/3/013. DOI

Battistini F., Sala A., Hospital A., Orozco M.. Sequence-dependent properties of the RNA duplex. J. Chem. Inf. Model. 2023;63:5259–5271. doi: 10.1021/acs.jcim.3c00741. PubMed DOI

Olson W. K., Young R. T., Czapla L.. DNA simulation benchmarks revealed with the accumulation of high-resolution structures. Biophys. Rev. 2024;16:275–284. doi: 10.1007/s12551-024-01198-2. PubMed DOI PMC

Lipfert J., Skinner G. M., Keegstra J. M., Hensgens T., Jager T., Dulin D., Köber M., Yu Z., Donkers S. P., Chou F. C.. et al. Double-stranded RNA under force and torque: Similarities to and striking differences from double-stranded DNA. Proc. Natl. Acad. Sci. U.S.A. 2014;111:15408–15413. doi: 10.1073/pnas.1407197111. PubMed DOI PMC

Furrer P., Bednar J., Stasiak A. Z., Katritch V., Michoud D., Stasiak A., Dubochet J.. Opposite effect of counterions on the persistence length of nicked and non-nicked DNA. J. Mol. Biol. 1997;266:711–721. doi: 10.1006/jmbi.1996.0825. PubMed DOI

Roldan-Pinero C., Luengo-Marquez J., Assenza S., Perez R.. Systematic comparison of atomistic force fields for the mechanical properties of double-stranded DNA. J. Chem. Theory Comput. 2024;20:2261–2272. doi: 10.1021/acs.jctc.3c01089. PubMed DOI PMC

Marin-Gonzalez A., Vihena J. G., Perez R., Moreno-Herrero F.. Understanding the mechanical response of double-stranded DNA and RNA under constant stretching force using all-atom molecular dynamics. Proc. Natl. Acad. Sci. U.S.A. 2017;114:7049–7054. doi: 10.1073/pnas.1705642114. PubMed DOI PMC

Marin-Gonzalez A., Vilhena J., Moreno-Herrero F., Perez R.. DNA crookedness regulates DNA mechanical properties at short length scales. Phys. Rev. Lett. 2019;122:048102. doi: 10.1103/physrevlett.122.048102. PubMed DOI

Trifonov, E. N. ; Tan, R. K. Z. ; Harvey, S. C. . In Structure and Expression; Olson, W. K. , Sarma, M. H. , Sarma, R. H. , Sundaralingam, M. , Eds.; Adenine Press, Inc.: Albany, NY, 1988; pp 243–254.

Vologodskaia M., Vologodskii A.. Contribution of the intrinsic curvature to measured DNA persistence length. J. Mol. Biol. 2002;317:205–2013. doi: 10.1006/jmbi.2001.5366. PubMed DOI

Schurr J. M.. A quantitative model of a cooperative two-state equilibrium in DNA: experimental tests, insights, and predictions. Q. Rev. Biophys. 2021;54:e5. doi: 10.1017/s0033583521000032. PubMed DOI

Noy A., Golestanian R.. Length scale dependence of DNA mechanical properties. Phys. Rev. Lett. 2012;109:228101. doi: 10.1103/PhysRevLett.109.228101. PubMed DOI

Higham N. J.. Computing a nearest symmetric positive semidefinite matrix. Linear Algebra Appl. 1988;103:103–118. doi: 10.1016/0024-3795(88)90223-6. DOI

Dans P. D., Danilane L., Ivani I., Drsata T., Lankas F., Hospital A., Walther J., Pujagut R. I., Battistini F., Gelpi J. L.. et al. Long-timescale dynamics of the Drew-Dickerson dodecamer. Nucleic Acids Res. 2016;44:4052–4066. doi: 10.1093/nar/gkw264. PubMed DOI PMC

Tereshko V., Minasov G., Egli M.. The Dickerson-Drew B-DNA dodecamer revisited at atomic resolution. J. Am. Chem. Soc. 1999;121:470–471. doi: 10.1021/ja9832919. DOI

Liu J., Subirana J. A.. Structure of d­(CGCGAATTCGCG) in the presence of Ca2+ ions. J. Biol. Chem. 1999;274:24749–24752. doi: 10.1074/jbc.274.35.24749. PubMed DOI

Sines C. C., McFail-Isom L., Howerton S. B., VanDerveer D., Williams L. D.. Cations mediate B-DNA conformational heterogeneity. J. Am. Chem. Soc. 2000;122:11048–11056. doi: 10.1021/ja002244p. DOI

Johansson E., Parkinson G., Neidle S.. A new crystal form for the dodecamer C-G-C-G-A-A-T-T-C-G-C-G: Symmetry effects on sequence-dependent DNA structure. J. Mol. Biol. 2000;300:551–561. doi: 10.1006/jmbi.2000.3907. PubMed DOI

Joshi R., Passner J. M., Rohs R., Jain R., Sosinsky A., Crickmore M. A., Jacob V., Aggarwal A., Honig B., Mann R. S.. Functional specificity of a Hox protein mediated by the recognition of minor groove structure. Cell. 2007;131:530–543. doi: 10.1016/j.cell.2007.09.024. PubMed DOI PMC

Segal E., Widom J.. Poly­(dA:dT) tracts: major determinants of nucleosome organization. Curr. Opin. Struct. Biol. 2009;19:65–71. doi: 10.1016/j.sbi.2009.01.004. PubMed DOI PMC

Haran T. E., Mohanty U.. The unique structure of A-tracts and intrinsic DNA bending. Q. Rev. Biophys. 2009;42:41–81. doi: 10.1017/S0033583509004752. PubMed DOI

Raveh-Sadka T., Levo M., Shabi U., Shany B., Keren L., Lotan-Pompan M., Zeevi D., Sharon D., Weinberger A., Segal E.. Manipulating nucleosome disfavoring sequences allows fine-tune regulation of gene expression in yeast. Nat. Genet. 2012;44:743–750. doi: 10.1038/ng.2305. PubMed DOI

Dr ata T., pa kova N., Jure ka P., Zgarbova M., poner J., Lanka F.. Mechanical properties of symmetric and asymmetric DNA A-tracts: Implications for looping and nucleosome positioning. Nucleic Acids Res. 2014;42:7383–7394. doi: 10.1093/nar/gku338. PubMed DOI PMC

Shimizu M., Mori T., Sakurai T., Shindo H.. Destabilization of nucleosomes by an unusual DNA conformation adopted by poly­(dA).poly­(dT) tracts in vivo . EMBO J. 2000;19:3358–3365. doi: 10.1093/emboj/19.13.3358. PubMed DOI PMC

Davey C. A., Sargent D. F., Luger K., Maeder A. W., Richmond T. J.. Solvent mediated interactions in the structure of the nucleosome core particle at 1.9 A resolution. J. Mol. Biol. 2002;319:1097–1113. doi: 10.1016/S0022-2836(02)00386-8. PubMed DOI

Bishop T. C.. Geometry of the nucleosomal DNA superhelix. Biophys. J. 2008;95:1007–1017. doi: 10.1529/biophysj.107.122853. PubMed DOI PMC

Strahs D., Schlick T.. A-tract bending: Insights into experimental structures by computational models. J. Mol. Biol. 2000;301:643–663. doi: 10.1006/jmbi.2000.3863. PubMed DOI

Stefl R., Wu H., Ravindranathan S., Sklenar V., Feigon J.. DNA A-tract bending in three dimensions: Solving the dA4T4 vs. dT4A4 conundrum. Proc. Natl. Acad. Sci. U.S.A. 2004;101:1177–1182. doi: 10.1073/pnas.0308143100. PubMed DOI PMC

Lankas F., Spackova N., Moakher M., Enkhbayar P., Sponer J.. A measure of bending in nucleic acids structures applied to A-tract DNA. Nucleic Acids Res. 2010;38:3414–3422. doi: 10.1093/nar/gkq001. PubMed DOI PMC

Stellwagen E., Peters J. P., Maher III L. J., Stellwagen N. C.. DNA A-tracts are not curved in solutions containing high concentrations of monovalent cations. Biochemistry. 2013;52:4138–4148. doi: 10.1021/bi400118m. PubMed DOI PMC

Kuhrova P., Mlynsky V., Zgarbova M., Krepl M., Bussi G., Best R. B., Otyepka M., Sponer J., Banas P.. Improving the performance of the Amber RNA force field by tuning the hydrogen-bonding interactions. J. Chem. Theory Comput. 2019;15:3288–3305. doi: 10.1021/acs.jctc.8b00955. PubMed DOI PMC

Mlynsky V., Janecek M., Kuhrova P., Frohlking T., Otyepka M., Bussi G., Banas P., Sponer J.. Toward convergence in folding simulations of RNA tetraloops: Comparison of enhanced sampling techniques and effects of force field modifications. J. Chem. Theory Comput. 2022;18:2642–2656. doi: 10.1021/acs.jctc.1c01222. PubMed DOI

Banas P., Mladek A., Otyepka M., Zgarbova M., Jurecka P., Svozil D., Lankas F., Sponer J.. Can we accurately describe the structure of adenine tracts in B-DNA? Reference quantum-chemical computations reveal overstabilization of stacking by molecular mechanics. J. Chem. Theory Comput. 2012;8:2448–2460. doi: 10.1021/ct3001238. PubMed DOI

Priyakumar U. D., MacKerell A. D. Jr.. Computational approaches for investigating base flipping in oligonucleotides. Chem. Rev. 2006;106:489–505. doi: 10.1021/cr040475z. PubMed DOI

Sanchez H. R.. Residence times from molecular dynamics simulations. J. Phys. Chem. B. 2022;126:8804–8812. doi: 10.1021/acs.jpcb.2c03756. PubMed DOI

Snoussi K., Leroy J.-L.. Imino proton exchange and base-pair kinetics in RNA duplexes. Biochemistry. 2001;40:8898–8904. doi: 10.1021/bi010385d. PubMed DOI

Harp J. M., Lybrand T. P., Pallan P. S., Coates L., Sullivan B., Egli M.. Cryo neutron crystallography demonstrates influence of RNA 2’-OH orientation on conformation, sugar pucker and water structure. Nucleic Acids Res. 2022;50:7721–7738. doi: 10.1093/nar/gkac577. PubMed DOI PMC

Darre L., Ivani I., Dans P. D., Gomez H., Hospital A., Orozco M.. Small details matter: The 2’-hydroxyl as a conformational switch in RNA. J. Am. Chem. Soc. 2016;138:16355–16363. doi: 10.1021/jacs.6b09471. PubMed DOI

Beck T. L., Carloni P., Asthagiri D. N.. All-atom biomolecular simulation in the exascale era. J. Chem. Theory Comput. 2024;20:1777–1782. doi: 10.1021/acs.jctc.3c01276. PubMed DOI

Carloni P., Sanbonmatsu K.. Exascale simulations and beyond. Curr. Opin. Struct. Biol. 2024;89:102939. doi: 10.1016/j.sbi.2024.102939. PubMed DOI

Li J., Zhou Y., Chen S.-J.. Embracing exascale computing in nucleic acid simulations. Curr. Opin. Struct. Biol. 2024;87:102847. doi: 10.1016/j.sbi.2024.102847. PubMed DOI PMC