Effect of Guanine to Inosine Substitution on Stability of
Canonical DNA and RNA Duplexes: Molecular Dynamics
Thermodynamics Integration Study

J 2013

Effect of Guanine to Inosine Substitution on Stability of Canonical DNA and RNA Duplexes: Molecular Dynamics Thermodynamics Integration Study

KREPL, Miroslav, Michal OTYEPKA, Pavel BANÁŠ and Jiří ŠPONER

Basic information

Original name

Effect of Guanine to Inosine Substitution on Stability of Canonical DNA and RNA Duplexes: Molecular Dynamics Thermodynamics Integration Study

Name in Czech

Vliv guanin -> inosin substituce na stabilitu kanonických DNA a RNA duplexů: Studie pomocí molekulové dynamiky a thermodynamické integrace.

Authors

KREPL, Miroslav (203 Czech Republic), Michal OTYEPKA (203 Czech Republic), Pavel BANÁŠ (203 Czech Republic) and Jiří ŠPONER (203 Czech Republic, guarantor, belonging to the institution)

Edition

JOURNAL OF PHYSICAL CHEMISTRY B, Washington, American Chemical Society, 2013, 1520-6106

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: 3.377

RIV identification code

RIV/00216224:14740/13:00067680

Organization unit

Central European Institute of Technology

DOI

http://dx.doi.org/10.1021/jp311180u

UT WoS

000315181600046

Keywords in English

FREE-ENERGY CALCULATIONS; PARTICLE MESH EWALD; ACID BASE-PAIRS; NUCLEIC-ACIDS; FORCE-FIELD; BIOMOLECULAR SIMULATIONS; SECONDARY STRUCTURE; HYDROGEN-BONDS; AMINO-GROUPS; A-RNA

Abstract

V originále

Guanine to inosine (G -> I) substitution has often been used to study various properties of nucleic acids. Inosine differs from guanine only by loss of the N2 amino group, while both bases have similar electrostatic potentials. Therefore, G -> I substitution appears to be optimally suited to probe structural and thermodynamics effects of single H-bonds and atomic groups. However, recent experiments have revealed substantial difference in free energy impact of G -> I substitution in the context of B-DNA and A-RNA canonical helices, suggesting that the free energy changes reflect context-dependent balance of energy contributions rather than intrinsic strength of a single Fl-bond. In the present study, we complement the experiments by free energy computations using thermodynamics integration method based on extended explicit solvent molecular dynamics simulations. The computations successfully reproduce the basic qualitative difference in free energy impact of G -> I substitution in B-DNA and A-RNA helices although the magnitude of the effect is somewhat underestimated. The computations, however, do not reproduce the salt dependence of the free energy changes. We tentatively suggest that the different effect of G -> I substitution in A-RNA and B-DNA may be related to different topologies of these helices, which affect the electrostatic interactions between the base pairs and the negatively charged backbone. Limitations of the computations are briefly discussed.

Links

ED1.1.00/02.0068, research and development project

Name: CEITEC - central european institute of technology

Citovat

KREPL, Miroslav, Michal OTYEPKA, Pavel BANÁŠ and Jiří ŠPONER. Effect of Guanine to Inosine Substitution on Stability of Canonical DNA and RNA Duplexes: Molecular Dynamics Thermodynamics Integration Study. JOURNAL OF PHYSICAL CHEMISTRY B. Washington: American Chemical Society, 2013, vol. 117, No 6, p. 1872-1879. ISSN 1520-6106. Available from: https://dx.doi.org/10.1021/jp311180u.

@article{1084029,
   author = {Krepl, Miroslav and Otyepka, Michal and Banáš, Pavel and Šponer, Jiří},
   article_location = {Washington},
   article_number = {6},
   doi = {http://dx.doi.org/10.1021/jp311180u},
   keywords = {FREE-ENERGY CALCULATIONS; PARTICLE MESH EWALD; ACID BASE-PAIRS; NUCLEIC-ACIDS; FORCE-FIELD; BIOMOLECULAR SIMULATIONS; SECONDARY STRUCTURE; HYDROGEN-BONDS; AMINO-GROUPS; A-RNA},
   language = {eng},
   issn = {1520-6106},
   journal = {JOURNAL OF PHYSICAL CHEMISTRY B},
   title = {Effect of Guanine to Inosine Substitution on Stability of Canonical DNA and RNA Duplexes: Molecular Dynamics Thermodynamics Integration Study},
   url = {http://pubs.acs.org/doi/pdf/10.1021/jp311180u},
   volume = {117},
   year = {2013}
}

TY  - JOUR
ID  - 1084029
AU  - Krepl, Miroslav - Otyepka, Michal - Banáš, Pavel - Šponer, Jiří
PY  - 2013
TI  - Effect of Guanine to Inosine Substitution on Stability of Canonical DNA and RNA Duplexes: Molecular Dynamics Thermodynamics Integration Study
JF  - JOURNAL OF PHYSICAL CHEMISTRY B
VL  - 117
IS  - 6
SP  - 1872-1879
EP  - 1872-1879
PB  - American Chemical Society
SN  - 15206106
KW  - FREE-ENERGY CALCULATIONS
KW  - PARTICLE MESH EWALD
KW  - ACID BASE-PAIRS
KW  - NUCLEIC-ACIDS
KW  - FORCE-FIELD
KW  - BIOMOLECULAR SIMULATIONS
KW  - SECONDARY STRUCTURE
KW  - HYDROGEN-BONDS
KW  - AMINO-GROUPS
KW  - A-RNA
UR  - http://pubs.acs.org/doi/pdf/10.1021/jp311180u
L2  - http://pubs.acs.org/doi/pdf/10.1021/jp311180u
N2  - Guanine to inosine (G -> I) substitution has often been used to study various properties of nucleic acids. Inosine differs from guanine only by loss of the N2 amino group, while both bases have similar electrostatic potentials. Therefore, G -> I substitution appears to be optimally suited to probe structural and thermodynamics effects of single H-bonds and atomic groups. However, recent experiments have revealed substantial difference in free energy impact of G -> I substitution in the context of B-DNA and A-RNA canonical helices, suggesting that the free energy changes reflect context-dependent balance of energy contributions rather than intrinsic strength of a single Fl-bond. In the present study, we complement the experiments by free energy computations using thermodynamics integration method based on extended explicit solvent molecular dynamics simulations. The computations successfully reproduce the basic qualitative difference in free energy impact of G -> I substitution in B-DNA and A-RNA helices although the magnitude of the effect is somewhat underestimated. The computations, however, do not reproduce the salt dependence of the free energy changes. We tentatively suggest that the different effect of G -> I substitution in A-RNA and B-DNA may be related to different topologies of these helices, which affect the electrostatic interactions between the base pairs and the negatively charged backbone. Limitations of the computations are briefly discussed.
ER  -

KREPL, Miroslav, Michal OTYEPKA, Pavel BANÁŠ and Jiří ŠPONER. Effect of Guanine to Inosine Substitution on Stability of Canonical DNA and RNA Duplexes: Molecular Dynamics Thermodynamics Integration Study. \textit{JOURNAL OF PHYSICAL CHEMISTRY B}. Washington: American Chemical Society, 2013, vol.~117, No~6, p.~1872-1879. ISSN~1520-6106. Available from: https://dx.doi.org/10.1021/jp311180u.

Detailed Information on Publication Record