20.500.12556/DKUM-94603 Molekulska dinamika vezave cianidina na SIRT6: pomembnost za človeško zdravje diplomsko delo univerzitetnega študijskega programa I. stopnje Molecular dynamics of cyanidin binding to SIRT6: importance for human health Z namenom, ne le podaljšati življensko dobo, temveč tudi ohraniti daljše obdobje zdravja človeka, je vedno več raziskav usmerjenih v razvoj naravnih modulatorjev encimske aktivnosti človeškega sirtuina 6 (SIRT6). Ta namreč sodeluje pri več celičnih procesih, povezanih s staranjem, ki bi jih lahko regulirali s pomočjo naravnih modulatorjev, flavonoidov. Med slednje spadata cianidin ter njegov glukozid cianidin-3-O-glukozid (Cy3G). S pomočjo računalniških orodij smo simulirali molekulske dinamike (MD) vezave teh ligandov na kompleks SIRT6 in adenozin difosfat(ADP)-riboze. Z analizo vrednosti RMSD ter časovnega deleža vodikovih vezi simulacije MD smo preučili stabilnost obeh ligandov v kompleksih ter določili stabilnejšega izmed obeh. Izkazalo se je, da se oba liganda stabilizirata v proteinskih kompleksih po 50 ns simulacije MD, a je ta stabilizacija pri cianidinu močnejša. Analiza vrednosti RMSD za izključno liganda je prav tako pokazala, da je cianidin stabilnejši izmed obeh. Dokončno potrditev tega smo dokazali z analizo vodikovih vezi med ligandoma ter SIRT6. Ugotovili smo, da se pri Cy3G karakteristične vodikove vezi vzpostavijo po 20 ns simulacije MD oziroma po zvišanju vrednosti RMSD. To poveča razliko med eksperimentalno določeno prvotno strukturo ter končno strukturo proteinskega kompleksa SIRT6–Cy3G. To dokazuje, da je cianidin boljša izbira za razvoj selektivnih in učinkovitih modulatorjev SIRT6, a je zaradi razlik v farmakokinetiki smotrno preučiti oba liganda. Te ugotovitve bi lahko vodile v raziskovanje in razvoj terapevtskih učinkovin za zdravljenje bolezni staranja, kot je na primer rak. With the aim of not only extending life expectancy, but also maintaining human health for longer periods of time, an increasing amount of research is focused on the development of natural modulators of the enzymatic activity of human sirtuin 6 (SIRT6). This enzyme is involved in several cellular processes related to aging, which could be regulated with the help of natural modulators, flavonoids. These also include cyanidin and its glucoside, cyanidin-3-O-glucoside (Cy3G). Using computational methods, we simulated the molecular dynamics (MD) of the binding of these ligands to the SIRT6 and adenosine diphosphate ribose (ADP-ribose) complex. By analyzing the RMSD values and the time portion of hydrogen bonds in the MD simulation, we studied the stability of both ligands in the complexes and determined which of the two was more stable. It turned out that both ligands stabilize in protein complexes after 50 ns of MD simulation, but this stabilization is stronger with cyanidin. An analysis of the RMSD values for the ligand alone also showed that cyanidin is the more stable of the two. We confirmed this conclusively by analyzing the hydrogen bonds between the ligands and SIRT6. We found that hydrogen bonds are formed in Cy3G only after 20 ns of MD simulation, or after an increase in the RMSD value. This increases the difference between the experimentally determined initial structure and the final structure of the SIRT6–Cy3G protein complex. This proves that cyanidin is a better choice for the development of selective and effective SIRT6 modulators, but both should be considered due to different pharmacokinetics. These findings could lead to the research and development of therapeutic agents for the treatment of age-related diseases, such as cancer. bolezni staranja SIRT6 molekulska dinamika naravni modulatorji encimov cianidin cianidin-3-O-glukozid age-related diseases SIRT6 molecular dynamics natural enzyme modulators cyanidin cyanidin-3-O-glucoside true true false [G. Dimnik] Slovenski jezik Angleški jezik Diplomsko delo/naloga 2025-08-22 10:15:49 2025-09-18 11:37:21 2025-09-30 03:33:25 0000-00-00 00:00:00 2025 0 Maribor 0 Maribor 1 spletni vir (1 datoteka PDF (X, 32 f.)) 0000-00-00 NiDoloceno NiDoloceno NiDoloceno 0000-00-00 0000-00-00 0000-00-00 577.151(043.2) 250796291 UN_Dimnik_Gasper_2025.pdf UN_Dimnik_Gasper_2025.pdf 1 2ED6B5B0EC46FA0A597C441D8CE16A28 009f25004842e2523237bfdfeb1a350b3da8241e01aeff9cfacecdb755609be3 bcd170eb-7fa9-11f0-a8d1-00155d000105 https://dk.um.si/Dokument.php?lang=slv&id=196008 Fakulteta za kemijo in kemijsko tehnologijo 0 0 0