20.500.12556/DKUM-99645 Preučevanje polifenolov iz timijana kot modulatorjev receptorja PPARγ s pomočjo molekulskega sidranja in simulacij molekulske dinamike Investigation of thyme polyphenols as modulators of the receptor PPARγ using molecular docking and molecular dynamics simulations Diplomsko delo obravnava luteolin, polifenol iz timijana (Thymus vulgaris), kot potencialni modulator jedrnega receptorja PPARγ . Receptor PPARγ ima ključno vlogo pri uravnavanju presnove glukoze in lipidov, zato predstavlja pomembno tarčo pri zdravljenju sladkorne bolezni tipa 2. Sintetični agonisti PPARγ sicer učinkovito povečajo občutljivost na inzulin, vendar so povezani z resnimi stranskimi učinki, med katerimi so povečanje telesne mase, edemi in srčno-žilni zapleti. Naravni polifenoli kot selektivni modulatorji PPARγ tako predstavljajo bolj varno alternativo. V diplomskem delu smo za preučevanje vezave luteolina na ligand-vezavno domeno PPARγ uporabili sodobne računalniške metode, ki vključujejo molekulsko sidranje, simulacije molekulske dinamike in metodo linearne interakcijske energije (LIE). Molekulsko sidranje smo izvedli s programom CmDock, simulacije molekulske dinamike dolžine 200 ns pa z programom NAMD na superračunalniku HPC Vega. Trajektorije smo analizirali s programoma VMD in PyMol, vezavno prosto energijo pa smo izračunali z metodo LIE z empiričnima parametroma α = 0,18 in β = 0,33. Rezultati kažejo, da se luteolin verjetno veže na receptor PPARγ. Ugotovili smo, da je kompleks luteolin-PPARγ med simulacijo molekulske dinamike stabilen ter da luteolin tvori ključne medmolekulske interakcije z aminokislinskimi preostanki na vezavnem mestu receptorja. Na podlagi negativne vrednosti vezavne proste energije sklepamo, da bi luteolin lahko deloval kot selektivni modulator PPARγ. This diploma thesis investigates luteolin, a polyphenol from thyme (Thymus vulgaris), as a potential modulator of the receptor PPARγ. PPARγ plays a key role in regulating glucose and lipid metabolism and, therefore, represents an important therapeutic target in the treatment of type 2 diabetes. Synthetic PPARγ agonists effectively enhance insulin sensitivity, however, they are associated with serious side effects, including weight gain, oedema, and cardiovascular complications. Naturally occurring polyphenols s thus represent a safer alternative as selective PPARγ modulators. To investigate the binding of luteolin to the PPARγ ligand-binding domain, we employed modern computational techniques, including molecular docking, molecular dynamics simulations, and the Linear Interaction Energy (LIE) method. Molecular docking was performed using CmDock, while 200 ns molecular dynamics simulations were conducted using NAMD on the HPC Vega supercomputer. Trajectories were analysed in VMD and PyMOL, and the binding free energy was calculated using the LIE method with empirical parameters α = 0.18 and β = 0.33. The results indicate that luteolin likely binds to PPARγ. We found that the luteolin–PPARγ complex remains stable throughout the molecular dynamics simulation and that luteolin forms specific intermolecular interactions within the receptor binding site amino-acid residues. Based on the negative binding free energy value, we conclude that luteolin may act as a selective PPARγ modulator. PPARγ polifenoli luteolin timijan molekulsko sidranje molekulska dinamika PPARγ polyphenols lutheolin thyme molecular docking molecular dynamics true true false Slovenski jezik Angleški jezik Diplomsko delo/naloga 2026-08-21 19:02:47 2026-09-14 11:40:54 2026-09-15 03:06:05 0000-00-00 00:00:00 2026 0 Maribor 0 0000-00-00 NiDoloceno NiDoloceno NiDoloceno 0000-00-00 0000-00-00 0000-00-00 VS_Pantner_Ana_Lee_2026.pdf VS_Pantner_Ana_Lee_2026.pdf 1 93DC335A69E3429D1E125FB60DCC502A 6a30599164ece27fdb9eece1f3f05b087438a981a45c577d345e9042abac0e31 5319b0cc-b01c-11f1-81c4-00155d0001be https://dk.um.si/Dokument.php?lang=slv&id=212327 Fakulteta za kemijo in kemijsko tehnologijo 0 0 0