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.

Základní údaje

Originální název

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

Autoři

STADLBAUER, Petr (203 Česká republika), Lukáš TRANTÍREK (203 Česká republika, domácí), Thomas E. CHEATHAM III. (840 Spojené státy), Jaroslav KOČA (203 Česká republika, domácí) a Jiří ŠPONER (203 Česká republika, garant, domácí)

Vydání

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

Další údaje

Jazyk

angličtina

Typ výsledku

Článek v odborném periodiku

Obor

10600 1.6 Biological sciences

Stát vydavatele

Francie

Utajení

není předmětem státního či obchodního tajemství

Odkazy

URL

Impakt faktor

Impact factor: 2.963

Kód RIV

RIV/00216224:14740/14:00074073

Organizační jednotka

Středoevropský technologický institut

DOI

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

UT WoS

000343022400004

Klíčová slova anglicky

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

Štítky

kontrola MP, MP, rivok, SCOPUS

Příznaky

Mezinárodní význam, Recenzováno

Změněno: 15. 7. 2015 09:13, Martina Prášilová

Anotace

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.

Návaznosti

ED1.1.00/02.0068, projekt VaV

Název: CEITEC - central european institute of technology

GA13-28310S, projekt VaV

Název: Evolučně konzervované strukturní vlastnosti centromerické a telomerické DNA

Investor: Grantová agentura ČR, Evolucne konzervované strukturní vlastnosti centromerické a telomerické DNA

2535, interní kód MU

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

Investor: EMBO (European Molecular Biology Organization), Cellular Structural Biology of non-B DNA Motifs in Human Genome

322104, interní kód MU

Název: Environmentally COntrolled POlymorphism of non-B DNA structures (Akronym: ECOPOD)

Investor: Evropská unie, Environmentally COntrolled POlymorphism of non-B DNA structures, Lidé

Citovat

STADLBAUER, Petr, Lukáš TRANTÍREK, Thomas E. CHEATHAM III., Jaroslav KOČA a 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, roč. 105c, October, s. 22-35. ISSN 0300-9084. Dostupné z: 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 a 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, roč.~105c, October, s.~22-35. ISSN~0300-9084. Dostupné z: https://dx.doi.org/10.1016/j.biochi.2014.07.009.

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