prikaz prve stranice dokumenta Molekulsko uklapanje potencijalnih inhibitora na protein ABCG2
  Download
PDF 3.17 MB
master's thesis
Molekulsko uklapanje potencijalnih inhibitora na protein ABCG2
Zagreb: University of Zagreb, Faculty of Science, 2021. urn:nbn:hr:217:191282
Radman, Katarina
University of Zagreb
Faculty of Science
Department of Biology

Institutional repository: Repository of the Faculty of Science

Cite this document

Radman, K. (2021). Molekulsko uklapanje potencijalnih inhibitora na protein ABCG2 (Master's thesis). Zagreb: University of Zagreb, Faculty of Science. Retrieved from https://urn.nsk.hr/urn:nbn:hr:217:191282

Radman, Katarina. "Molekulsko uklapanje potencijalnih inhibitora na protein ABCG2." Master's thesis, University of Zagreb, Faculty of Science, 2021. https://urn.nsk.hr/urn:nbn:hr:217:191282

Radman, Katarina. "Molekulsko uklapanje potencijalnih inhibitora na protein ABCG2." Master's thesis, University of Zagreb, Faculty of Science, 2021. https://urn.nsk.hr/urn:nbn:hr:217:191282

Radman, K. (2021). 'Molekulsko uklapanje potencijalnih inhibitora na protein ABCG2', Master's thesis, University of Zagreb, Faculty of Science, accessed 21 May 2024, https://urn.nsk.hr/urn:nbn:hr:217:191282

Radman K. Molekulsko uklapanje potencijalnih inhibitora na protein ABCG2 [Master's thesis]. Zagreb: University of Zagreb, Faculty of Science; 2021 [cited 2024 May 21] Available at: https://urn.nsk.hr/urn:nbn:hr:217:191282

K. Radman, "Molekulsko uklapanje potencijalnih inhibitora na protein ABCG2", Master's thesis, University of Zagreb, Faculty of Science, Zagreb, 2021. Available at: https://urn.nsk.hr/urn:nbn:hr:217:191282

Metadata
TitleMolekulsko uklapanje potencijalnih inhibitora na protein ABCG2
Title (english)Docking study of interactions between the ABCG2 protein and potential inhibitors
AuthorKatarina Radman
MentorBranimir Bertoša (mentor)
Committee memberBranimir Bertoša (predsjednik povjerenstva)
Committee memberIvana Ivančić Baće (član povjerenstva)
Committee memberMartina Šeruga Musić (član povjerenstva)
Committee memberBiljana Balen (član povjerenstva)
GranterUniversity of Zagreb
Faculty of Science
(Department of Biology)
Zagreb
Defense date and country2021-07-08, Croatia
Scientific / art field,
discipline and subdiscipline		NATURAL SCIENCES
Biology
Abstract
Protein ABCG2 je transmembranski protein koji djeluje kao pumpa za izbacivanje raznih endogenih supstrata. Prekomjerna ekspresija proteina ABCG2 u stanicama karcinoma jedan je od glavnih uzroka otpornosti stanica karcinoma na mnoge lijekove. Recentna istraživanja pokazala su potencijal adamantil-supstituiranih diaza-krunastih etera (DAC) kao inhibitora proteina ABCG2. U sklopu ovog diplomskog rada računalno je istraženo vezanje različitih DAC na protein ABCG2 te je njihovo vezanje uspoređeno s vezanjem literaturno poznatih inhibitora i supstrata proteina ABCG2. Vezanje DAC te poznatih inhibitora i supstrata proteina ABCG2 provedeno je metodom molekulskog uklapanja. Napravljena su dva računa molekulskog uklapanja za svaki ligand. Prvi račun obuhvaćao je cijeli protein ABCG2, dok je drugi račun obuhvaćao samo mjesto vezanja supstrata i inhibitora (šupljna 1). Temeljem provedenog računalnog istraživanja vezanja liganada na protein ABCG2 utvrđeno je da DAC-amidi imaju povoljniji afinitet vezanja za šupljinu 1 od poznatih inhibitora proteina ABCG2. Spojevi DAC-amidi se za razliku od poznatih inhibitora i supstrata proteina ABCG2 ne vežu duboko unutar šupljine 1 te ne ostvaruju značajnije interakcije s aminokiselinom koja je literaturno apostrofirana kao važna za vezanje (Phe 439). Budući da se DAC-amidi također vežu za mjesto prijelaza iz domene NBD u domenu TMD predložena su dva potencijalna načina inhibicije proteina ABCG2.
Abstract (english)
ABCG2 is a transmembrane protein pump that protects tissue from entrance of unwanted substances. However, ABCG2 affects the pharmacokinetics of commonly used drugs, and its expression correlates with poor treatment outcome of certain cancers. Recent studies have revealed that adamantylsubstituted diaza- (DAC) crown compounds show inhibitory potential towards ABCG2. The aim of this graduate thesis was to study the binding interactions between DAC crown coumpounds and ABCG2. To evaluate the binding potential of DAC crown compounds, a study of binding interactions between known ABCG2 inhibitors and ABCG2 has been made in parallel. The binding interactions were investigated using two molecular docking simulations. In the first simulation ligands were docked onto the whole ABCG2 protein whilst in the second simulation ligands were docked into the substrate binding site (Cavity 1). Results obtained in the scope of this thesis suggest that DAC-amids have lower binding energy than known inhibitors bound in Cavity 1 and that they also bind to the NBD-TMD interface. Binding of DAC-amids in Cavity 1 is shallower and they do not interact with Phe 439, which is literary known to be important for substrate binding. For the reasons stated, two potential ways of ABCG2 inhibition by DAC-amids have been proposed.
Keywords
Keywords (english)
Languagecroatian
URN:NBNurn:nbn:hr:217:191282
Study programmeTitle: Molecular Biology
Study programme type: university
Study level: graduate
Academic / professional title: magistar/magistra molekularne biologije (magistar/magistra molekularne biologije)
Type of resourceText
File originBorn digital
Access conditionsOpen access
Terms of useLicence In copyright icon
Created on2021-07-22 12:28:37