prikaz prve stranice dokumenta Analysis of DNA methyltransferase DNMT1 structure and function and development of noncovalent inhibitors using computational methods
  Download
PDF 2.8 MB
master's thesis
Analysis of DNA methyltransferase DNMT1 structure and function and development of noncovalent inhibitors using computational methods
2023. urn:nbn:hr:193:785350
Morović, Viktor
University of Rijeka
Faculty of Biotechnology and Drug Development

Cite this document

Morović, V. (2023). Analysis of DNA methyltransferase DNMT1 structure and function and development of noncovalent inhibitors using computational methods (Master's thesis). Rijeka: University of Rijeka. Retrieved from https://urn.nsk.hr/urn:nbn:hr:193:785350

Morović, Viktor. "Analysis of DNA methyltransferase DNMT1 structure and function and development of noncovalent inhibitors using computational methods." Master's thesis, University of Rijeka, 2023. https://urn.nsk.hr/urn:nbn:hr:193:785350

Morović, Viktor. "Analysis of DNA methyltransferase DNMT1 structure and function and development of noncovalent inhibitors using computational methods." Master's thesis, University of Rijeka, 2023. https://urn.nsk.hr/urn:nbn:hr:193:785350

Morović, V. (2023). 'Analysis of DNA methyltransferase DNMT1 structure and function and development of noncovalent inhibitors using computational methods', Master's thesis, University of Rijeka, accessed 29 April 2024, https://urn.nsk.hr/urn:nbn:hr:193:785350

Morović V. Analysis of DNA methyltransferase DNMT1 structure and function and development of noncovalent inhibitors using computational methods [Master's thesis]. Rijeka: University of Rijeka; 2023 [cited 2024 April 29] Available at: https://urn.nsk.hr/urn:nbn:hr:193:785350

V. Morović, "Analysis of DNA methyltransferase DNMT1 structure and function and development of noncovalent inhibitors using computational methods", Master's thesis, University of Rijeka, Rijeka, 2023. Available at: https://urn.nsk.hr/urn:nbn:hr:193:785350

Please login to the repository to save this object to your list.
Metadata
TitleAnalysis of DNA methyltransferase DNMT1 structure and function and development of noncovalent inhibitors using computational methods
Title (croatian)Analiza strukture i funkcije DNA metiltransferaze DNMT1 i razvoj nekovalentnih inhibitora koristeći računalne metode
AuthorViktor Morović
MentorŽeljko Svedružić (mentor)
MentorJurica Novak (komentor)
Committee memberJurica Novak (predsjednik povjerenstva)
Committee memberRozi Andretić Waldowski (član povjerenstva)
Committee memberNela Malatesti (član povjerenstva)
Committee memberKatarina Kapuralin (član povjerenstva)
GranterUniversity of Rijeka
(Faculty of Biotechnology and Drug Development)
Rijeka
Defense date and country2023-07-14, Croatia
Scientific / art field,
discipline and subdiscipline		BIOTECHNICAL SCIENCES
Biotechnology
Abstract
DNA methyltransferase 1 (DNMT1) is an enzyme that plays an essential role in epigenetic regulation of mammalian genetic expression. Dysregulation of methylation processes can lead to various pathological conditions, which in recent years ,lead to extensive study of structure and function of DNMT1. DNMT1 has multiple forms dependant of the stage of DNA methylation, which posses limitations in both discovery and modification of new drugs. With use of in silico methods we sought to identify drug like compounds capable of binding to, and inhibiting the function of DNMT1. Analysis of molecular dynamics (MD) simulations showed stronger binding of SAH to all three DNMT1 proteins (4WXX, 3PTA and 4DA4), compared to tested compounds. Two compounds moved from the SAH binding site during initial simulations, for which they were excluded from further research. Tested compounds adhere to the Lipinski rule but lack the formation of hydrogen bonds with DNMT1, compared to SAH. Future research should use the potential of π- π stacking interaction with residues inside SAH binding pocket.
Abstract (croatian)
DNA metiltransferaza 1 (DNMT1) je enzim koji ima ključnu ulogu u epigenetskoj regulaciji genske ekspresije kod sisavaca. Disregulacija procesa metilacije može dovesti do raznih patoloških stanja, što je posljednjih godina dovelo do opsežnog proučavanja strukture I funkcije DNMT1. DNMT1 postoji u više oblika ovisno o stupnju metilacije DNA, što ograničava mogućnost u otkrivanju i modifikaciji novih lijekova. Korištenjem in silico metoda nastojali smo identificirati spojeve slične lijekovima koji se mogu vezati I inhibirati funkciju DNMT1. Analiza simulacija molekularne dinamike (MD pokazale su jače vezanje SAH na sva tri proteina DNMT1 (4WXX, 3PTA i 4DA4), u usporedbi s testiranim spojevima. Dva spoja pomaknula su se s veznog mjesta SAH tijekom početnih simulacija, zbog čega su isključena iz daljnjeg istraživanja. Ispitani spojevi pridržavaju se Lipinskog pravila, ali stvaraju manje vodikovih veza s DNMT1, u usporedbi sa SAH. Buduća bi istraživanja trebala iskoristiti potencijal π-π interakcija s aminokiselinskim ostacima unutar SAH veznog džepa.
Keywords
Keywords (croatian)
Languagecroatian
URN:NBNurn:nbn:hr:193:785350
Study programmeTitle: Medicinal chemistry
Study programme type: university
Study level: graduate
Academic / professional title: magistar/magistra medicinske kemije (magistar/magistra medicinske kemije)
Type of resourceText
File originBorn digital
Access conditionsOpen access
Terms of useLicence In copyright icon
Created on2023-10-11 12:38:34