Evaluation of autophagy inhibition to combat cancer: (vanadium complex)–protein interactions, parameterization, and validation of a new force field
The result's identifiers
Result code in IS VaVaI
<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F62690094%3A18470%2F23%3A50020366" target="_blank" >RIV/62690094:18470/23:50020366 - isvavai.cz</a>
Result on the web
<a href="https://link.springer.com/article/10.1007/s00894-023-05530-7" target="_blank" >https://link.springer.com/article/10.1007/s00894-023-05530-7</a>
DOI - Digital Object Identifier
<a href="http://dx.doi.org/10.1007/s00894-023-05530-7" target="_blank" >10.1007/s00894-023-05530-7</a>
Alternative languages
Result language
angličtina
Original language name
Evaluation of autophagy inhibition to combat cancer: (vanadium complex)–protein interactions, parameterization, and validation of a new force field
Original language description
Autophagy has drawn attention from the scientific community, mainly because of its significant advantages over chemotherapeutic processes. One of these advantages is its direct action on cancer cells, avoiding possible side effects, unlike chemotherapy, which reaches tumor cells and affects healthy cells in the body, leading to a great loss in the quality of life of patients. In this way, it is known that vanadium complex (VC) [VO(oda)(phen)] has proven inhibition effect on autophagy process in pancreatic cancer cells. Keeping that in mind, molecular dynamics (MD) simulations can be considered excellent strategies to investigate the interaction of metal complexes and their biological targets. However, simulations of this type are strongly dependent on the appropriate choice of force field (FF). Therefore, this work proposes the development of AMBER FF parameters for VC, having a minimum energy structure as a starting point, obtained through DFT calculations with B3LYP/def2-TZVP level of theory plus ECP for the vanadium atom. An MD simulation in vacuum was performed to validate the developed FF. From the structural analyses, satisfying values of VC bond lengths and angles were obtained, where a good agreement with the experimental data and the quantum reference was found. The RMSD analysis showed an average of only 0.3%. Finally, we performed docking and MD (120 ns) simulations with explicit solvent between VC and PI3K. Overall, our findings encourage new parameterizations of metal complexes with significant biological applications, as well as allow to contribute to the elucidation of the complex process of autophagy. Graphical abstract: [Figure not available: see fulltext.] © 2023, The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.
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
10610 - Biophysics
Result continuities
Project
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Continuities
I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace
Others
Publication year
2023
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
29
Issue of the periodical within the volume
4
Country of publishing house
US - UNITED STATES
Number of pages
17
Pages from-to
"Article number: 123"
UT code for WoS article
000961041700002
EID of the result in the Scopus database
2-s2.0-85151477121