Relative Stability of Different DNA Guanine Quadruplex Stem
Topologies Derived Using Large-Scale Quantum-Chemical
Computations

J 2013

Relative Stability of Different DNA Guanine Quadruplex Stem Topologies Derived Using Large-Scale Quantum-Chemical Computations

ŠPONER, Jiří, Arnošt MLÁDEK, Naděžda ŠPAČKOVÁ, Xiaohui H. CANG, Thomas E. CHEATHAM et. al.

Basic information

Original name

Relative Stability of Different DNA Guanine Quadruplex Stem Topologies Derived Using Large-Scale Quantum-Chemical Computations

Authors

ŠPONER, Jiří (203 Czech Republic, guarantor, belonging to the institution), Arnošt MLÁDEK (203 Czech Republic, belonging to the institution), Naděžda ŠPAČKOVÁ (203 Czech Republic, belonging to the institution), Xiaohui H. CANG (156 China), Thomas E. CHEATHAM (840 United States of America) and Stefan GRIMME (276 Germany)

Edition

Journal of the American Chemical Society, WASHINGTON, American Chemical Society, 2013, 0002-7863

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: 11.444

RIV identification code

RIV/00216224:14740/13:00069530

Organization unit

Central European Institute of Technology

DOI

http://dx.doi.org/10.1021/ja402525c

UT WoS

000321541800040

Keywords in English

DENSITY-FUNCTIONAL THEORY; MOLECULAR-DYNAMICS SIMULATIONS; SUGAR-PHOSPHATE BACKBONE; APPROXIMATE COULOMB POTENTIALS; HUMAN TELOMERIC QUADRUPLEXES; ZETA VALENCE QUALITY; AUXILIARY BASIS-SETS; AMBER FORCE-FIELD; NUCLEIC-ACIDS; CRYSTAL-STRUCTURE

Abstract

V originále

We provide theoretical predictions of the intrinsic stability of different arrangements of guanine quadruplex (G-DNA) stems. Most computational studies of nucleic acids have applied Molecular Mechanics (MM) approaches using simple pairwise-additive force fields. The principle limitation of such calculations is the highly approximate nature of the force fields. In this study, we for the first time apply accurate QM computations (DFT-D3 with large atomic orbital basis sets) to essentially complete DNA building blocks, seven different folds of the cation stabilized two quartet G-DNA stem, each having more than 250 atoms. The solvent effects are approximated by COSMO continuum solvent We reveal sizable differences between MM and QM descriptions of relative energies of different G-DNA stems, which apparently reflect approximations of the DNA force field. Using the QM energy data, we propose correction to earlier free energy estimates of relative stabilities of different parallel, hybrid, and antiparallel G-stem folds based on classical simulations. The new energy ranking visibly improves the agreement between theory and experiment We predict the 5'-anti-anti-3' GpG dinucleotide step to be the most stable one, closely followed by the 5'-syn-anti-3' step. The results are in good agreement with known experimental structures of 2-, 3-, and 4-quartet G-DNA stems. Besides providing specific results for G-DNA, our study highlights basic limitations of force field modeling of nucleic acids. Although QM computations have their own limitations, mainly the lack of conformational sampling and the approximate description of the solvent, they can substantially improve the quality of calculations currently relying exclusively on force fields.

Links

ED1.1.00/02.0068, research and development project

Name: CEITEC - central european institute of technology

Citovat

ŠPONER, Jiří, Arnošt MLÁDEK, Naděžda ŠPAČKOVÁ, Xiaohui H. CANG, Thomas E. CHEATHAM and Stefan GRIMME. Relative Stability of Different DNA Guanine Quadruplex Stem Topologies Derived Using Large-Scale Quantum-Chemical Computations. Journal of the American Chemical Society. WASHINGTON: American Chemical Society, 2013, vol. 135, No 26, p. 9785-9796. ISSN 0002-7863. Available from: https://dx.doi.org/10.1021/ja402525c.

@article{1124229,
   author = {Šponer, Jiří and Mládek, Arnošt and Špačková, Naděžda and Cang, Xiaohui H. and Cheatham, Thomas E. and Grimme, Stefan},
   article_location = {WASHINGTON},
   article_number = {26},
   doi = {http://dx.doi.org/10.1021/ja402525c},
   keywords = {DENSITY-FUNCTIONAL THEORY; MOLECULAR-DYNAMICS SIMULATIONS; SUGAR-PHOSPHATE BACKBONE; APPROXIMATE COULOMB POTENTIALS; HUMAN TELOMERIC QUADRUPLEXES; ZETA VALENCE QUALITY; AUXILIARY BASIS-SETS; AMBER FORCE-FIELD; NUCLEIC-ACIDS; CRYSTAL-STRUCTURE},
   language = {eng},
   issn = {0002-7863},
   journal = {Journal of the American Chemical Society},
   title = {Relative Stability of Different DNA Guanine Quadruplex Stem Topologies Derived Using Large-Scale Quantum-Chemical Computations},
   url = {http://pubs.acs.org/doi/abs/10.1021/ja402525c},
   volume = {135},
   year = {2013}
}

TY  - JOUR
ID  - 1124229
AU  - Šponer, Jiří - Mládek, Arnošt - Špačková, Naděžda - Cang, Xiaohui H. - Cheatham, Thomas E. - Grimme, Stefan
PY  - 2013
TI  - Relative Stability of Different DNA Guanine Quadruplex Stem Topologies Derived Using Large-Scale Quantum-Chemical Computations
JF  - Journal of the American Chemical Society
VL  - 135
IS  - 26
SP  - 9785-9796
EP  - 9785-9796
PB  - American Chemical Society
SN  - 00027863
KW  - DENSITY-FUNCTIONAL THEORY
KW  - MOLECULAR-DYNAMICS SIMULATIONS
KW  - SUGAR-PHOSPHATE BACKBONE
KW  - APPROXIMATE COULOMB POTENTIALS
KW  - HUMAN TELOMERIC QUADRUPLEXES
KW  - ZETA VALENCE QUALITY
KW  - AUXILIARY BASIS-SETS
KW  - AMBER FORCE-FIELD
KW  - NUCLEIC-ACIDS
KW  - CRYSTAL-STRUCTURE
UR  - http://pubs.acs.org/doi/abs/10.1021/ja402525c
L2  - http://pubs.acs.org/doi/abs/10.1021/ja402525c
N2  - We provide theoretical predictions of the intrinsic stability of different arrangements of guanine quadruplex (G-DNA) stems. Most computational studies of nucleic acids have applied Molecular Mechanics (MM) approaches using simple pairwise-additive force fields. The principle limitation of such calculations is the highly approximate nature of the force fields. In this study, we for the first time apply accurate QM computations (DFT-D3 with large atomic orbital basis sets) to essentially complete DNA building blocks, seven different folds of the cation stabilized two quartet G-DNA stem, each having more than 250 atoms. The solvent effects are approximated by COSMO continuum solvent We reveal sizable differences between MM and QM descriptions of relative energies of different G-DNA stems, which apparently reflect approximations of the DNA force field. Using the QM energy data, we propose correction to earlier free energy estimates of relative stabilities of different parallel, hybrid, and antiparallel G-stem folds based on classical simulations. The new energy ranking visibly improves the agreement between theory and experiment We predict the 5'-anti-anti-3' GpG dinucleotide step to be the most stable one, closely followed by the 5'-syn-anti-3' step. The results are in good agreement with known experimental structures of 2-, 3-, and 4-quartet G-DNA stems. Besides providing specific results for G-DNA, our study highlights basic limitations of force field modeling of nucleic acids. Although QM computations have their own limitations, mainly the lack of conformational sampling and the approximate description of the solvent, they can substantially improve the quality of calculations currently relying exclusively on force fields.
ER  -

ŠPONER, Jiří, Arnošt MLÁDEK, Naděžda ŠPAČKOVÁ, Xiaohui H. CANG, Thomas E. CHEATHAM and Stefan GRIMME. Relative Stability of Different DNA Guanine Quadruplex Stem Topologies Derived Using Large-Scale Quantum-Chemical Computations. \textit{Journal of the American Chemical Society}. WASHINGTON: American Chemical Society, 2013, vol.~135, No~26, p.~9785-9796. ISSN~0002-7863. Available from: https://dx.doi.org/10.1021/ja402525c.

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