Base Pair Fraying in Molecular Dynamics Simulations of DNA and
RNA

J 2014

Base Pair Fraying in Molecular Dynamics Simulations of DNA and RNA

ZGARBOVÁ, Marie, Michal OTYEPKA, Jiří ŠPONER, Filip LANKAŠ, Petr JUREČKA et. al.

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

Language

English

Type of outcome

Článek v odborném periodiku

Field of Study

10403 Physical chemistry

Country of publisher

United States of America

Confidentiality degree

není předmětem státního či obchodního tajemství

References:

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

Abstract

V originále

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.

Citovat

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.

@article{1200024,
   author = {Zgarbová, Marie and Otyepka, Michal and Šponer, Jiří and Lankaš, Filip and Jurečka, Petr},
   article_location = {Washington},
   article_number = {8},
   doi = {http://dx.doi.org/10.1021/ct500120v},
   keywords = {QUANTUM-CHEMICAL COMPUTATIONS; NUCLEIC-ACID STRUCTURES; AMBER FORCE-FIELD; B-DNA; THERMODYNAMIC PARAMETERS; PROTON-EXCHANGE; QUADRUPLEX DNA; IMINO PROTON; DODECAMER; SEQUENCE},
   language = {eng},
   issn = {1549-9618},
   journal = {Journal of Chemical Theory and Computation},
   title = {Base Pair Fraying in Molecular Dynamics Simulations of DNA and RNA},
   url = {http://pubs.acs.org/doi/abs/10.1021/ct500120v},
   volume = {10},
   year = {2014}
}

TY  - JOUR
ID  - 1200024
AU  - Zgarbová, Marie - Otyepka, Michal - Šponer, Jiří - Lankaš, Filip - Jurečka, Petr
PY  - 2014
TI  - Base Pair Fraying in Molecular Dynamics Simulations of DNA and RNA
JF  - Journal of Chemical Theory and Computation
VL  - 10
IS  - 8
SP  - 3177-3189
EP  - 3177-3189
PB  - American Chemical Society
SN  - 15499618
KW  - QUANTUM-CHEMICAL COMPUTATIONS
KW  - NUCLEIC-ACID STRUCTURES
KW  - AMBER FORCE-FIELD
KW  - B-DNA
KW  - THERMODYNAMIC PARAMETERS
KW  - PROTON-EXCHANGE
KW  - QUADRUPLEX DNA
KW  - IMINO PROTON
KW  - DODECAMER
KW  - SEQUENCE
UR  - http://pubs.acs.org/doi/abs/10.1021/ct500120v
L2  - http://pubs.acs.org/doi/abs/10.1021/ct500120v
N2  - 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.
ER  -

ZGARBOVÁ, Marie, Michal OTYEPKA, Jiří ŠPONER, Filip LANKAŠ and Petr JUREČKA. Base Pair Fraying in Molecular Dynamics Simulations of DNA and RNA. \textit{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.

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