Triplex intermediates in folding of human telomeric
quadruplexes probed by microsecond-scale molecular dynamics
simulations

J 2014

Triplex intermediates in folding of human telomeric quadruplexes probed by microsecond-scale molecular dynamics simulations

STADLBAUER, Petr, Lukáš TRANTÍREK, Thomas E. CHEATHAM III., Jaroslav KOČA, Jiří ŠPONER et. al.

Basic information

Original name

Triplex intermediates in folding of human telomeric quadruplexes probed by microsecond-scale molecular dynamics simulations

Authors

STADLBAUER, Petr (203 Czech Republic), Lukáš TRANTÍREK (203 Czech Republic, belonging to the institution), Thomas E. CHEATHAM III. (840 United States of America), Jaroslav KOČA (203 Czech Republic, belonging to the institution) and Jiří ŠPONER (203 Czech Republic, guarantor, belonging to the institution)

Edition

Biochimie, Paris, ELSEVIER FRANCE-EDITIONS SCIENTIFIQUES MEDICALES ELSEVIER, 2014, 0300-9084

Other information

Language

English

Type of outcome

Článek v odborném periodiku

Field of Study

10600 1.6 Biological sciences

Country of publisher

France

Confidentiality degree

není předmětem státního či obchodního tajemství

References:

URL

Impact factor

Impact factor: 2.963

RIV identification code

RIV/00216224:14740/14:00074073

Organization unit

Central European Institute of Technology

DOI

http://dx.doi.org/10.1016/j.biochi.2014.07.009

UT WoS

000343022400004

Keywords in English

G-DNA folding; Molecular dynamics; Quadruplex; Telomere; Triplex

Abstract

V originále

We have carried out extended set of mu s-scale explicit solvent MD simulations of all possible G-triplexes which can participate in folding pathways of the human telomeric quadruplex. Our study accumulates almost 60 mu s of simulation data, which is by about three orders of magnitude larger sampling compared to the earlier simulations of human telomeric G-DNA triplexes. Starting structures were obtained from experimental quadruplex structures by deleting either the first or the last strand. The life-times of antiparallel triplexes with lateral and diagonal loops are at least on mu s-scale, which should be sufficient to contribute to the folding pathways. However, the triplex states may involve structures with various local deviations from the ideal triplexes, such as strand tilting and various alternative and incomplete triads. The simulations reveal easy rearrangements between lateral and diagonal loop triplex topologies. Propeller loops of antiparallel triplexes may to certain extent interfere with the G-triplexes but these structures are still viable candidates to participate in the folding. In contrast, all-parallel all-anti triplexes are very unstable and are unlikely to contribute to the folding. Although our simulations demonstrate that antiparallel G-triplexes, if folded, would have life-times sufficient to participate in the quadruplex folding, the results do not rule out the possibility that the G-triplexes are out-competed by other structures not included in our study. Among them, numerous possible misfolded structures containing guanine quartets can act as off-path intermediates with longer life-times than the triplexes. Besides analyzing the structural dynamics of a diverse set of G-DNA triplexes, we also provide a brief discussion of the limitations of the simulation methodology, which is necessary for proper understanding of the simulation data. (C) 2014 The Authors. Published by Elsevier Masson SAS.

Links

ED1.1.00/02.0068, research and development project

Name: CEITEC - central european institute of technology

GA13-28310S, research and development project

Name: Evolučně konzervované strukturní vlastnosti centromerické a telomerické DNA

Investor: Czech Science Foundation

2535, interní kód MU

Name: Cellular Structural Biology of non-B DNA Motifs in Human Genome

Investor: EMBO (European Molecular Biology Organization)

322104, interní kód MU

Name: Environmentally COntrolled POlymorphism of non-B DNA structures (Acronym: ECOPOD)

Investor: European Union, People

Citovat

STADLBAUER, Petr, Lukáš TRANTÍREK, Thomas E. CHEATHAM III., Jaroslav KOČA and Jiří ŠPONER. Triplex intermediates in folding of human telomeric quadruplexes probed by microsecond-scale molecular dynamics simulations. Biochimie. Paris: ELSEVIER FRANCE-EDITIONS SCIENTIFIQUES MEDICALES ELSEVIER, 2014, 105c, October, p. 22-35. ISSN 0300-9084. Available from: https://dx.doi.org/10.1016/j.biochi.2014.07.009.

@article{1205389,
   author = {Stadlbauer, Petr and Trantírek, Lukáš and Cheatham III., Thomas E. and Koča, Jaroslav and Šponer, Jiří},
   article_location = {Paris},
   article_number = {October},
   doi = {http://dx.doi.org/10.1016/j.biochi.2014.07.009},
   keywords = {G-DNA folding; Molecular dynamics; Quadruplex; Telomere; Triplex},
   language = {eng},
   issn = {0300-9084},
   journal = {Biochimie},
   title = {Triplex intermediates in folding of human telomeric quadruplexes probed by microsecond-scale molecular dynamics simulations},
   url = {http://www.sciencedirect.com/science/article/pii/S0300908414001874},
   volume = {105c},
   year = {2014}
}

TY  - JOUR
ID  - 1205389
AU  - Stadlbauer, Petr - Trantírek, Lukáš - Cheatham III., Thomas E. - Koča, Jaroslav - Šponer, Jiří
PY  - 2014
TI  - Triplex intermediates in folding of human telomeric quadruplexes probed by microsecond-scale molecular dynamics simulations
JF  - Biochimie
VL  - 105c
IS  - October
SP  - 22-35
EP  - 22-35
PB  - ELSEVIER FRANCE-EDITIONS SCIENTIFIQUES MEDICALES ELSEVIER
SN  - 03009084
KW  - G-DNA folding
KW  - Molecular dynamics
KW  - Quadruplex
KW  - Telomere
KW  - Triplex
UR  - http://www.sciencedirect.com/science/article/pii/S0300908414001874
L2  - http://www.sciencedirect.com/science/article/pii/S0300908414001874
N2  - We have carried out extended set of mu s-scale explicit solvent MD simulations of all possible G-triplexes which can participate in folding pathways of the human telomeric quadruplex. Our study accumulates almost 60 mu s of simulation data, which is by about three orders of magnitude larger sampling compared to the earlier simulations of human telomeric G-DNA triplexes. Starting structures were obtained from experimental quadruplex structures by deleting either the first or the last strand. The life-times of antiparallel triplexes with lateral and diagonal loops are at least on mu s-scale, which should be sufficient to contribute to the folding pathways. However, the triplex states may involve structures with various local deviations from the ideal triplexes, such as strand tilting and various alternative and incomplete triads. The simulations reveal easy rearrangements between lateral and diagonal loop triplex topologies. Propeller loops of antiparallel triplexes may to certain extent interfere with the G-triplexes but these structures are still viable candidates to participate in the folding. In contrast, all-parallel all-anti triplexes are very unstable and are unlikely to contribute to the folding. Although our simulations demonstrate that antiparallel G-triplexes, if folded, would have life-times sufficient to participate in the quadruplex folding, the results do not rule out the possibility that the G-triplexes are out-competed by other structures not included in our study. Among them, numerous possible misfolded structures containing guanine quartets can act as off-path intermediates with longer life-times than the triplexes. Besides analyzing the structural dynamics of a diverse set of G-DNA triplexes, we also provide a brief discussion of the limitations of the simulation methodology, which is necessary for proper understanding of the simulation data. (C) 2014 The Authors. Published by Elsevier Masson SAS.
ER  -

STADLBAUER, Petr, Lukáš TRANTÍREK, Thomas E. CHEATHAM III., Jaroslav KOČA and Jiří ŠPONER. Triplex intermediates in folding of human telomeric quadruplexes probed by microsecond-scale molecular dynamics simulations. \textit{Biochimie}. Paris: ELSEVIER FRANCE-EDITIONS SCIENTIFIQUES MEDICALES ELSEVIER, 2014, 105c, October, p.~22-35. ISSN~0300-9084. Available from: https://dx.doi.org/10.1016/j.biochi.2014.07.009.

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