Complexity of Guanine Quadruplex Unfolding Pathways Revealed by Atomistic Pulling Simulations

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F68081707%3A_____%2F23%3A00574511" target="_blank" >RIV/68081707:_____/23:00574511 - isvavai.cz</a>

Nalezeny alternativní kódy

RIV/61989100:27740/23:10254096

Výsledek na webu

<a href="https://pubs.acs.org/doi/10.1021/acs.jcim.3c00171" target="_blank" >https://pubs.acs.org/doi/10.1021/acs.jcim.3c00171</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1021/acs.jcim.3c00171" target="_blank" >10.1021/acs.jcim.3c00171</a>

Jazyk výsledku

angličtina

Název v původním jazyce

Complexity of Guanine Quadruplex Unfolding Pathways Revealed by Atomistic Pulling Simulations

Popis výsledku v původním jazyce

Guanine quadruplexes (GQs) are non-canonical nucleicacid structuresinvolved in many biological processes. GQs formed in single-strandedregions often need to be unwound by cellular machinery, so their mechanochemicalproperties are important. Here, we performed steered molecular dynamicssimulations of human telomeric GQs to study their unfolding. We examinedfour pulling regimes, including a very slow setup with pulling velocityand force load accessible to high-speed atomic force microscopy. Weidentified multiple factors affecting the unfolding mechanism, i.e.,:(i) the more the direction of force was perpendicular to the GQ channelaxis (determined by GQ topology), the more the base unzipping mechanismhappened, (ii) the more parallel the direction of force was, GQ openingand cross-like GQs were more likely to occur, (iii) strand slippagemechanism was possible for GQs with an all-anti patternin a strand, and (iv) slower pulling velocity led to richer structuraldynamics with sampling of more intermediates and partial refoldingevents. We also identified that a GQ may eventually unfold after aforce drop under forces smaller than those that the GQ withstood beforethe drop. Finally, we found out that different unfolding intermediatescould have very similar chain end-to-end distances, which revealssome limitations of structural interpretations of single-moleculespectroscopic data.

Název v anglickém jazyce

Complexity of Guanine Quadruplex Unfolding Pathways Revealed by Atomistic Pulling Simulations

Popis výsledku anglicky

Guanine quadruplexes (GQs) are non-canonical nucleicacid structuresinvolved in many biological processes. GQs formed in single-strandedregions often need to be unwound by cellular machinery, so their mechanochemicalproperties are important. Here, we performed steered molecular dynamicssimulations of human telomeric GQs to study their unfolding. We examinedfour pulling regimes, including a very slow setup with pulling velocityand force load accessible to high-speed atomic force microscopy. Weidentified multiple factors affecting the unfolding mechanism, i.e.,:(i) the more the direction of force was perpendicular to the GQ channelaxis (determined by GQ topology), the more the base unzipping mechanismhappened, (ii) the more parallel the direction of force was, GQ openingand cross-like GQs were more likely to occur, (iii) strand slippagemechanism was possible for GQs with an all-anti patternin a strand, and (iv) slower pulling velocity led to richer structuraldynamics with sampling of more intermediates and partial refoldingevents. We also identified that a GQ may eventually unfold after aforce drop under forces smaller than those that the GQ withstood beforethe drop. Finally, we found out that different unfolding intermediatescould have very similar chain end-to-end distances, which revealssome limitations of structural interpretations of single-moleculespectroscopic data.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

10608 - Biochemistry and molecular biology

Projekt

<a href="/cs/project/GA21-23718S" target="_blank" >GA21-23718S: Studium fascinující fyzikální chemie DNA pomocí pokročilých výpočetních metod</a><br>

Návaznosti

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Rok uplatnění

2023

Kód důvěrnosti údajů

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Název periodika

Journal of Chemical Information and Modeling

ISSN

1549-9596

e-ISSN

1549-960X

Svazek periodika

63

Číslo periodika v rámci svazku

15

Stát vydavatele periodika

US - Spojené státy americké

Počet stran výsledku

16

Strana od-do

4716-4731

Kód UT WoS článku

001030479000001

EID výsledku v databázi Scopus

2-s2.0-85166539054