Vanadium complex as a potential modulator of the autophagic mechanism through proteins PI3K and ULK1: development, validation and biological implications of a specific force field for [VO(bpy)2Cl]

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F62690094%3A18470%2F24%3A50020615" target="_blank" >RIV/62690094:18470/24:50020615 - isvavai.cz</a>

Výsledek na webu

<a href="https://www.tandfonline.com/doi/full/10.1080/07391102.2023.2250453" target="_blank" >https://www.tandfonline.com/doi/full/10.1080/07391102.2023.2250453</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1080/07391102.2023.2250453" target="_blank" >10.1080/07391102.2023.2250453</a>

Jazyk výsledku

angličtina

Název v původním jazyce

Vanadium complex as a potential modulator of the autophagic mechanism through proteins PI3K and ULK1: development, validation and biological implications of a specific force field for [VO(bpy)2Cl]

Popis výsledku v původním jazyce

The modulation of autophagy has been presented as a very useful strategy in anticancer treatments. In this sense, the vanadium complex (VC) bis(2,2&apos;-bipyridine)chlorooxovanadium(IV), [VO(bpy)2Cl], is known for its ability to induce autophagy in triple-negative breast cancer cells (TNBC). An excellent resource to investigate the role of VC in the induction of autophagy is to make use of Molecular Dynamics (MD) simulations. However, until now, the scarcity of force field parameters for the VC prevented a reliable analysis. The autophagy signaling pathway starts with the PI3K protein and ends with ULK1. Therefore, in the first stage of this work, we developed a new AMBER force field for the VC (VCFF) from a quantum structure, obtained by DFT calculations. In the second stage, the VCFF was validated through structural analyses. From this, it was possible to investigate, through docking and MD (200 ns), the performance of the PI3K-VC and ULK1-VC systems (third stage). The analyses of this last stage involved RMSD, hydrogen bonds, RMSF and two pathways for the modulation of autophagy. In general, this work fills in the absence of force field parameters (FF) for VC by proposing an efficient and new FF, in addition to investigating, at the molecular level, how VC is able to induce autophagy in TNBC cells. This study encourages new parameterizations of metallic complexes and contributes to the understanding of the duality of autophagic processes. Communicated by Ramaswamy H. Sarma. © 2023 Informa UK Limited, trading as Taylor &amp; Francis Group.

Název v anglickém jazyce

Vanadium complex as a potential modulator of the autophagic mechanism through proteins PI3K and ULK1: development, validation and biological implications of a specific force field for [VO(bpy)2Cl]

Popis výsledku anglicky

The modulation of autophagy has been presented as a very useful strategy in anticancer treatments. In this sense, the vanadium complex (VC) bis(2,2&apos;-bipyridine)chlorooxovanadium(IV), [VO(bpy)2Cl], is known for its ability to induce autophagy in triple-negative breast cancer cells (TNBC). An excellent resource to investigate the role of VC in the induction of autophagy is to make use of Molecular Dynamics (MD) simulations. However, until now, the scarcity of force field parameters for the VC prevented a reliable analysis. The autophagy signaling pathway starts with the PI3K protein and ends with ULK1. Therefore, in the first stage of this work, we developed a new AMBER force field for the VC (VCFF) from a quantum structure, obtained by DFT calculations. In the second stage, the VCFF was validated through structural analyses. From this, it was possible to investigate, through docking and MD (200 ns), the performance of the PI3K-VC and ULK1-VC systems (third stage). The analyses of this last stage involved RMSD, hydrogen bonds, RMSF and two pathways for the modulation of autophagy. In general, this work fills in the absence of force field parameters (FF) for VC by proposing an efficient and new FF, in addition to investigating, at the molecular level, how VC is able to induce autophagy in TNBC cells. This study encourages new parameterizations of metallic complexes and contributes to the understanding of the duality of autophagic processes. Communicated by Ramaswamy H. Sarma. © 2023 Informa UK Limited, trading as Taylor &amp; Francis Group.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

10610 - Biophysics

Projekt

—

Návaznosti

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Rok uplatnění

2024

Kód důvěrnosti údajů

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

Název periodika

Journal of biomolecular structure and dynamics

ISSN

0739-1102

e-ISSN

1538-0254

Svazek periodika

42

Číslo periodika v rámci svazku

17

Stát vydavatele periodika

US - Spojené státy americké

Počet stran výsledku

15

Strana od-do

9118-9132

Kód UT WoS článku

001153740400001

EID výsledku v databázi Scopus

2-s2.0-85168702001