prikaz prve stranice dokumenta Molecular dynamics studies of DNA-DNA methyltransferase 1 complex structural changes during binding
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undergraduate thesis
Molecular dynamics studies of DNA-DNA methyltransferase 1 complex structural changes during binding
2019. urn:nbn:hr:193:043134
Koren, Rajna
University of Rijeka
Faculty of Biotechnology and Drug Development

Cite this document

Koren, R. (2019). Molecular dynamics studies of DNA-DNA methyltransferase 1 complex structural changes during binding (Undergraduate thesis). Rijeka: University of Rijeka. Retrieved from https://urn.nsk.hr/urn:nbn:hr:193:043134

Koren, Rajna. "Molecular dynamics studies of DNA-DNA methyltransferase 1 complex structural changes during binding." Undergraduate thesis, University of Rijeka, 2019. https://urn.nsk.hr/urn:nbn:hr:193:043134

Koren, Rajna. "Molecular dynamics studies of DNA-DNA methyltransferase 1 complex structural changes during binding." Undergraduate thesis, University of Rijeka, 2019. https://urn.nsk.hr/urn:nbn:hr:193:043134

Koren, R. (2019). 'Molecular dynamics studies of DNA-DNA methyltransferase 1 complex structural changes during binding', Undergraduate thesis, University of Rijeka, accessed 12 December 2024, https://urn.nsk.hr/urn:nbn:hr:193:043134

Koren R. Molecular dynamics studies of DNA-DNA methyltransferase 1 complex structural changes during binding [Undergraduate thesis]. Rijeka: University of Rijeka; 2019 [cited 2024 December 12] Available at: https://urn.nsk.hr/urn:nbn:hr:193:043134

R. Koren, "Molecular dynamics studies of DNA-DNA methyltransferase 1 complex structural changes during binding", Undergraduate thesis, University of Rijeka, Rijeka, 2019. Available at: https://urn.nsk.hr/urn:nbn:hr:193:043134

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Metadata
TitleMolecular dynamics studies of DNA-DNA methyltransferase 1 complex structural changes during binding
Title (croatian)Analiza strukturnih promjena DNA-DNA metiltransferaza 1 kompleksa tijekom vezivanja pomoću molekularne dinamike
AuthorRajna Koren
MentorŽeljko Svedružić (mentor)
GranterUniversity of Rijeka
(Faculty of Biotechnology and Drug Development)
Rijeka
Defense date and country2019-09-23, Croatia
Scientific / art field,
discipline and subdiscipline		BIOTECHNICAL SCIENCES
Biotechnology
Abstract
Background: DNA methylation is the first and most enduring epigenetic mark, that acts as a fundamental mechanism in functional organization of human genome. Inhibitors and activators of DNA methylation can be used for genetic reprogramming of differentiated cells, or as tools for gene expression analysis. DNA substrates with guanine replaced by inosine at the target site showed an amazing 30 fold activation in methylation activity. Activation of mammalian DNA methyltransferase (Dnmt1) by inosine at the target base site was explored at the enzyme structure level in attempt to design activators of DNA methylation as novel drug-candidates. Results: Coarse grained molecular dynamics simulations showed that mouse DNA methyltransferase forms unusual guanine-guanine base pair that can stabilize the catalytic complex. The stabilizing complex breaks down when the guanine at the target site is replaced by inosine. Principal component analysis with Bio3D application showed that the stability of the active site structure can affect Zn-finger rich domain that is distant from the active site. Conclusion: Structural changes in Dnmt1-DNA complex showed that Zn-finger rich domains participate in stabilization of enzyme-DNA complex. The Zn-finger rich domain will be targeted in the future in silico drug design protocols in an attempt to design novel activators of DNA methylation in human cells.
Abstract (croatian)
Pozadina: DNA metilacija je prvi i najtrajniji epigenetički biljeg koji služi kao temeljni organizacijski mehanizam za ljudski genom. Inhibitori i aktivatori DNA metilacije mogu se koristiti za gensko reprogramiranje diferenciranih stanica ili kao alat za analizu genske ekspresije. Zamjena DNA supstrata s gvaninom, s DNA supstratom koji sadrži inozin na ciljnom mjestu pokazao je 30 puta veću aktivnost metilacije. Aktivacija DNA metiltransferaze 1 (Dnmt1) sisavaca od strane inozina na ciljnom mjestu istražena je na razini strukture enzima kako bi se potencijalno dizajnirali aktivatori DNA metilacije kao kandidati za nove lijekove. Rezultati: Simulacije molekularne dinamike koje koriste grubi model molekula pokazale su da mišja DNA metiltransfraza formira neobične gvanin-gvanin bazne parove koji mogu stabilizirati katalitički kompleks. Taj stabilizirajući kompleks se raspadne kada je gvanin zamjenjen s inozinom na ciljnom mjestu. Bio3D analiza komponenata pokazala je da stabilnost strukture aktivnog mjesta može utjecati na domenu bogatu “Zn-prst“ strukturama koja je udaljena od aktivnog mjesta. Zaključak: Strukturne promjene u DNA-Dnmt1 kompleksu pokazale su da domene bogate “Zn-prst“ strukturama sudjeluju u stabilizaciji enzim-DNA kompleksa. Domene bogate “Zn-prst“ strukturama predstavljaju potencijalne mete za buduće in silico protokole dizajna lijekova kako bi se dizajnirali novi aktivatori DNA metilacije u ljudskim stanicama.
Keywords
Keywords (croatian)
Languageenglish
URN:NBNurn:nbn:hr:193:043134
Study programmeTitle: Biotechnology and drug research
Study programme type: university
Study level: undergraduate
Academic / professional title: sveučilišni/a prvostupnik/prvostupnica biotehnologije i istraživanja lijekova (sveučilišni/a prvostupnik/prvostupnica biotehnologije i istraživanja lijekova)
Type of resourceText
File originBorn digital
Access conditionsAccess restricted to students and staff of home institution
Terms of useLicence In copyright icon
Created on2019-11-05 11:35:04