Base Pair Fraying in Molecular Dynamics Simulations of DNA and RNA

ZGARBOVÁ, Marie, Michal OTYEPKA, Jiří ŠPONER, Filip LANKAŠ and Petr JUREČKA. Base Pair Fraying in Molecular Dynamics Simulations of DNA and RNA. Journal of Chemical Theory and Computation. Washington: American Chemical Society, 2014, vol. 10, No 8, p. 3177-3189. ISSN 1549-9618. Available from: https://dx.doi.org/10.1021/ct500120v.

Basic information

• Original name: Base Pair Fraying in Molecular Dynamics Simulations of DNA and RNA
• Authors: ZGARBOVÁ, Marie, Michal OTYEPKA, Jiří ŠPONER, Filip LANKAŠ and Petr JUREČKA.
• Edition: Journal of Chemical Theory and Computation, Washington, American Chemical Society, 2014, 1549-9618.

Other information

• Original language: English
• Type of outcome: Article in a journal
• Field of Study: 10403 Physical chemistry
• Country of publisher: United States of America
• Confidentiality degree: is not subject to a state or trade secret
• WWW: URL
• Impact factor: Impact factor: 5.498
• Organization unit: Central European Institute of Technology
• Doi: http://dx.doi.org/10.1021/ct500120v
• UT WoS: 000340351200030
• Keywords in English: QUANTUM-CHEMICAL COMPUTATIONS; NUCLEIC-ACID STRUCTURES; AMBER FORCE-FIELD; B-DNA; THERMODYNAMIC PARAMETERS; PROTON-EXCHANGE; QUADRUPLEX DNA; IMINO PROTON; DODECAMER; SEQUENCE
• Tags: kontrola MP, MP, neMU
• Tags: International impact, Reviewed

Abstract

Terminal base pairs of DNA and RNA molecules in solution are known to undergo frequent transient opening events (fraying). Accurate modeling of this process is important because of its involvement in nucleic acid end recognition and enzymatic catalysis. In this article, we describe fraying in molecular dynamics simulations with the ff99bsc0, ff99bsc0 chi(OL3), and ff99bsc0 chi(OL4) force fields, both for DNA and RNA molecules. Comparison with the experiment showed that while some features of fraying are consistent with the available data, others indicate potential problems with the force field description. In particular, multiple noncanonical structures are formed at the ends of the DNA and RNA duplexes. Among them are tWC/sugar edge pair, C-H edge/Watson-Crick pair, and stacked geometries, in which the terminal bases are stacked above each other. These structures usually appear within the first tens to hundreds of nanoseconds and substantially limit the usefulness of the remaining part of the simulation due to geometry distortions that are transferred to several neighboring base pairs ("end effects"). We show that stability of the noncanonical structures in ff99bsc0 may be partly linked to inaccurate glycosidic (chi) torsion potentials that overstabilize the syn region and allow for rapid anti to syn transitions. The RNA refined glycosidic torsion potential chi(OL3) provides an improved description and substantially more stable MD simulations of RNA molecules. In the case of DNA, the chi(OL4) correction gives only partial improvement. None of the tested force fields provide a satisfactory description of the terminal regions, indicating that further improvement is needed to achieve realistic modeling of fraying in DNA and RNA molecules.