magistrsko delo
Adela Avdičević (Author), Urban Bren (Mentor)

Abstract

V magistrski nalogi smo uporabili sodobne računalniške pristope z namenom odkrivanja novih potencialnih zdravil proti virusu HIV-1, ki povzroča AIDS. Proteaza HIV-1, encim, ki je ključnega pomena za razmnoževanje virusa, predstavlja eno najpomembnejših tarč za razvoj protivirusnih zdravil. Zaradi naraščajoče odpornosti virusa na obstoječa zdravila je nujno iskanje novih in učinkovitih zaviralcev tega encima. Uporabili smo kombinacijo naprednih računalniških metod, vključno z virtualnim rešetanjem, molekulskim sidranjem in molekulsko dinamiko, da bi ocenili sposobnost rozmanola in njegovih derivatov za vezavo na proteazo HIV-1 ter njihovo potencialno učinkovitost kot zaviralcev tega encima. Za podrobnejšo analizo smo izbrali molekulo 1 (ZINC5733675), ki je med virtualnim rešetanjem pokazala največjo podobnost z rozmanolom, ter molekulo 25 (ZINC4377044), ki smo jo med molekulskim sidranjem identificirali kot najbolj obetavno, saj je dosegla najnižjo vezavno energijo in največje število interakcij med vsemi analiziranimi ligandi. Molekulsko dinamiko smo izvedli za rozmanol in oba izbrana derivata vezana na HIV-1 proteazo, da bi preučili njihov vzorec dinamične vezave, kot tudi stabilnost njihovih interakcij z aktivnim mestom proteaze v dinamičnih pogojih. Ugotovili smo, da se ligandi premaknejo bližje verigi B proteaze, kar potrjujejo močnejše interakcije in stabilnost vezave s to verigo. Rezultati te magistrske naloge predstavljajo pomemben korak k razumevanju vezave ligandov naravnega izvora na katalitično mesto in zaviranja delovanja proteaze HIV-1. Naši rezultati nakazujejo, da bi rozmanol in njegovi derivati lahko predstavljali učinkovito osnovo za razvoj novih zdravil proti HIV/AIDS-u. Kljub obetavnim računalniškim napovedim pa je za nadaljnji razvoj teh spojin kot zdravil potrebna dodatna eksperimentalna validacija.

Keywords

proteaza HIV-1;AIDS;rozmanol;virtualno rešetanje;molekulsko sidranje;molekulska dinamika;magistrske naloge;

Data

Language: Slovenian
Year of publishing:
Typology: 2.09 - Master's Thesis
Organization: UM FKKT - Faculty of Chemistry and Chemical Engineering
Publisher: [A. Avdičević]
UDC: 004.9:615.281.8.015(043.2)
COBISS: 217051651 Link will open in a new window
Views: 26
Downloads: 24
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Other data

Secondary language: English
Secondary title: The use of modern computational methods in the search for novel antiviral drugs
Secondary abstract: In the master's thesis, we employed modern computational approaches to discover new potential drugs against HIV-1, the virus that causes AIDS. HIV-1 protease, an enzyme crucial for viral replication, is one of the most important targets for antiviral drug development. Due to the increasing resistance of the virus to existing drugs, it is essential to find new and effective inhibitors of this enzyme. We used a combination of advanced computational methods, including virtual screening, molecular docking, and molecular dynamics, to evaluate the binding potential of rosmanol and its derivatives to HIV-1 protease and their potential effectiveness as enzyme inhibitors. For detailed analysis, we selected molecule 1 (ZINC5733675), which exhibited the greatest similarity to rosmanol during virtual screening, and molecule 25 (ZINC4377044), identified as the most promising structure during molecular docking due to its lowest binding energy and the highest number of interactions among all analysed ligands. We performed molecular dynamics for rosmanol and both selected derivatives bound to HIV-1 protease to examine their dynamic binding pattern and the stability of their interactions with the protease's active site under dynamic conditions. We found that the ligand moves closer to the protease chain B, confirming stronger interactions and binding stability with this chain. The results of this master's thesis represent an important step toward understanding the binding of natural compounds to the catalytic site and the inhibition of HIV-1 protease activity. Our findings suggest that rosmanol and its derivatives could serve as an effective basis for developing new drugs against HIV/AIDS. Despite promising computational predictions, further experimental validation is necessary for the continued development of these compounds as therapeutic agents.
Secondary keywords: HIV-1 protease;AIDS;rosmanol;virtual screening;molecular docking;molecular dynamics;
Type (COBISS): Master's thesis/paper
Thesis comment: Univ. v Mariboru, Fak. za kemijo in kemijsko tehnologijo
Pages: 1 spletni vir (1 datoteka PDF (XII, 78 f.))
ID: 24823851