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Albany 2015:Book of Abstracts

Albany 2015
Conversation 19
June 9-13 2015
©Adenine Press (2012)

Base Pair Fraying in Molecular Dynamics Simulations of Nucleic Acids as a Force Field Benchmark

Fraying of nucleic acids is a reversible process in which the terminal base pairs of duplex lose their base pairing and unstack from their neighbors, allowing frequent refolding of the terminal base pairs. Accurate modeling of this process is important because of its involvement in nucleic acid end recognition and enzymatic catalysis. Here, we describe fraying in molecular dynamics simulations with the ff99bsc0, ff99bsc0χOL3, and ff99bsc0χOL4 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. We show that stability of the noncanonical structures in ff99bsc0 may be partly linked to inaccurate glycosidic (χ) torsion potentials that overstabilize the syn region and allow for rapid anti to syn transitions. The RNA refined glycosidic torsion potential χOL3 provides an improved description and substantially more stable MD simulations of RNA molecules. In the case of DNA, the χOL4 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.

References
    Zgarbova, M., Otyepka, M., Sponer, J., Mladek, A., Banas, P., Cheatham, T. E. 3rd, & Jurecka, P. (2011). Refinement of the Cornell et al. Nucleic Acids Force Field Based on Reference Quantum Chemical Calculations of Glycosidic Torsion Profiles. J. Chem. Theory Comput., 7, 2886-2902.

    Krepl, M., Zgarbova, M., Stadlbauer, P., Otyepka, M., Banas, P., Koca, J.,Cheatham, T. E. 3rd, Jurecka, P., & Sponer, J. (2012). Reference Simulations of Noncanonical Nucleic Acids with Different chi Variants of the AMBER Force Field: Quadruplex DNA, Quadruplex RNA, and Z-DNA. J. Chem. Theory Comput., 8, 2506-2520.

    Zgarbova, M., Otyepka, M., Sponer, J., Lankas, F., & Jurecka, P. (2014). Base Pair Fraying in Molecular Dynamics Simulation of DNA and RNA. J. Chem. Theory Comput., 10, 3177-3189.

Marie Zgarbova1
Michal Otyepka 1
Jiri Sponer2
Filip Lankas 3
Petr Jurecka1

1Regional Centre of Advanced Technologies and Materials
Department of Physical Chemistry
Faculty of Science
Palacky University
17. listopadu 12
77146 Olomouc
Czech Republic
2Institute of Biophysics
Academy of Sciences of the Czech Republic
Kralovopolska 135
61265 Brno, Czech Republic
3Institute of Organic chemistry and Biochemistry
Academy of Sciences of the Czech Republic
Flemingovo nam. 2
16610 Prague, Czech Republic

Ph: (+420) 585 634 766
Fx: (+420) 585 634 761
marie.zgarbova@upol.cz