Exploring the potential of vanadium(IV) complex in autophagy activation: structural modifications, NMR calculations, and novel interactions with PI3Kγ
The result's identifiers
Result code in IS VaVaI
<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F62690094%3A18470%2F25%3A50022855" target="_blank" >RIV/62690094:18470/25:50022855 - isvavai.cz</a>
Result on the web
<a href="https://link.springer.com/article/10.1007/s00894-025-06549-8" target="_blank" >https://link.springer.com/article/10.1007/s00894-025-06549-8</a>
DOI - Digital Object Identifier
<a href="http://dx.doi.org/10.1007/s00894-025-06549-8" target="_blank" >10.1007/s00894-025-06549-8</a>
Alternative languages
Result language
angličtina
Original language name
Exploring the potential of vanadium(IV) complex in autophagy activation: structural modifications, NMR calculations, and novel interactions with PI3Kγ
Original language description
Context: The modulation of autophagy – inhibition or induction – has emerged as a promising strategy in cancer treatment, offering significant advantages over conventional chemotherapy. Previously, we demonstrated that the vanadium complex [VO(oda)(phen)] inhibits autophagy by activating the phosphoinositide 3-kinase gamma (PI3Kγ) protein. Given the therapeutic potential of autophagy modulation, we proposed structural modifications to this complex to achieve the opposite effect: autophagy activation by preventing PI3Kγ activation. In this context, this study aimed to perform structural modifications on the vanadium complex to elucidate and discuss new conformational implications and its role in the autophagic machinery. The AMBER force field (FF) was adapted for the modified vanadium complex (mVC), yielding excellent results in molecular dynamics (MD) simulations in vacuum, protein, and aqueous environments. The structural modifications successfully disrupted the interaction between [VO(oda)(phen)] and PI3Kγ, previously identified as a key factor in PI3Kγ activation. Consequently, PI3Kγ deactivation leads to a shift in the autophagy signaling pathway, promoting autophagy activation. Additionally, NMR calculations were performed to explore a novel role for mVC, broadening its potential applications. Methods: MD simulations were conducted at 800 ns using the AMBER program, while Molegro Virtual Docker (MVD) was employed for docking simulations. Optimization calculations (B3LYP/def2-TZVP and LANL2DZ ECP for V) and NMR calculations (PBE/IGLO-II and Wachters + f for V) were performed using Gaussian 09. The key frames from the MD simulations were selected using the OWSCA algorithm. Ligand and protein performance were evaluated through RMSD, RMSF, and hydrogen bond analyses, applying cutoff distances of 3.5 Å and 30°. © The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature 2025.
Czech name
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Czech description
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Classification
Type
J<sub>imp</sub> - Article in a specialist periodical, which is included in the Web of Science database
CEP classification
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OECD FORD branch
10406 - Analytical chemistry
Result continuities
Project
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Continuities
I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace
Others
Publication year
2025
Confidentiality
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů
Data specific for result type
Name of the periodical
Journal of Molecular Modeling
ISSN
1610-2940
e-ISSN
0948-5023
Volume of the periodical
31
Issue of the periodical within the volume
12
Country of publishing house
US - UNITED STATES
Number of pages
15
Pages from-to
"Article number: 344"
UT code for WoS article
001623224500001
EID of the result in the Scopus database
2-s2.0-105022789753