Modeliranje nekovalentnih interakcija u procesima solvatacije kvercetina i reorganizacije konformacije fragmenta U6 snRNA

master's thesis

• Title (english): Modelling of Non-covalent Interactions in the Processes of Quercetin Solvation and Conformational Reorganisation of a U6 snRNA Fragment
• Author: Frano Mihaljević
• Mentor: Viktor Pilepić (mentor)
• Committee member: Viktor Pilepić (predsjednik povjerenstva)
• Committee member: Monika Barbarić (član povjerenstva)
• Committee member: Cvijeta Jakobušić Brala (član povjerenstva)
• Granter: University of Zagreb; Faculty of Pharmacy and Biochemistry; (Department of physical chemistry); Zagreb
• Defense date and country: 2019-07-12, Croatia
• Scientific / art field, discipline and subdiscipline: BIOMEDICINE AND HEALTHCARE; Pharmacy; Pharmacy

Abstract

Istraživanja nekovalentnih interakcija na dva modela različitih biokemijski i biomedicinski važnih sustava: sustavu molekule
i odgovarajućih aniona kvercetina s okolnim molekulama vode te promjena konformacije fragmenta U6 snRNA u vodi
provedena su pomoću molekulsko dinamičkih i kvantno mehaničkih računskih metoda.
Računalno modeliranje solvatacije (hidratacije) sustava molekule i odgovarajućih aniona kvercetina s okolnim molekulama
vode provedeno je za sve strukture prisutne na fiziološkom pH pri čemu su te strukture smještene u kvadar ispunjen
molekulama vode u periodičkim uvjetima. Na takvom modelu, provedeni su računi molekulske dinamike u vremenu od 20
ns, a iz dobivenih trajektorija izračunati su prosječni reducirani gradijenti gustoće i termalni fluktuacijski indeksi. Vizualna
prezentacija dobivenih rezultata omogućila je analizu prosječnih nekovalentnih interakcija molekula kvercetina s
fluktuirajućom okolinom molekula vode pri čemu je utvrđeno da je solvatni kavez molekula otapala (vode) oko karbonilnih i
OH skupina kvercetina vrlo čvrst, slabiji oko B prstena te najslabiji ispod i iznad ravnine A i C prstena te se može
pretpostaviti da je na tome mjestu sterički olakšan pristup reaktivnom radikalu u antioksidativnoj reakciji kvercetina.
Računalno modeliranje sustava fragmenta U6 snRNA u vodi provedeno je za dvije različite konformacije koje se razlikuju u
orijentaciji U80 koje su povezane s biološkom funkcijom tog fragmenta. Strukture su smještene u kvadar ispunjen
molekulama vode u periodičkim uvjetima te su na takvom modelu provedeni računi molekulske dinamike u vremenu od 20
ns, a iz dobivenih trajektorija izračunati su prosječni reducirani gradijenti gustoće, termalni fluktuacijski indeksi te kvantno
mehanički računi elektronske gustoće za reprezentativne strukture. Vizualna prezentacija dobivenih rezultata omogućila je
detaljnu analizu prosječnih nekovalentnih interakcija baze U80 fragmenta U6 s fluktuirajućom okolinom koja uključuje
ostale okolne baze, molekule vode i natrijeve ione tijekom procesa preklapanja u okviru reorganizacije konformacije
fragmenta U6, pri čemu se utvrdilo da u cijelom procesu sudjeluju vodikove veze između baza i okolnih molekula vode te πinterakcije između baza.

Abstract (english)

The research of non-covalent interactions was performed on two models of different biochemically and biomedically
important systems: a system of quercetin molecule and the corresponding anions in a water solution and a system of the U6 fragment of snRNA in a water solution, by using molecular dynamic and quantum chemistry calculation methods.
Computer modelling of the solvation (hydration) of the system containing quercetin molecule with surrounding water
molecules was performed for all of the quercetin structures present in physiological pH. The structures were placed in a box filled with water molecules. Molecular dynamics calculations were performed for a time of 20 ns in periodic boundary
conditions. Values of average reduced density gradient and thermal fluctuation indices were calculated from the obtained
trajectories. Visual presentation of calculated results enabled the analysis of the average non-covalent interactions of
quercetin molecule with fluctuating environment made of water molecules. It was found that the solvent cages around
carbonyl and OH functional groups are very tight, weak around the B ring and weaker above and below A and C ring planes. It can be assumed that the approach of the reactive radical in the antioxidative reaction of quercetin is sterically enabled around these areas. Computer modelling of the U6 snRNA fragment system in water was performed for two different fragment conformations that differ in the orientation of U80 base. These conformations are related to the biological function of the fragment. Structures were placed in a box filled with water molecules. Molecular dynamics calculations were performed for a time of 20 ns in periodic boundary conditions. Visual presentation of calculated results enabled the analysis of the average noncovalent interactions of U80 base of the U6 RNA with the fluctuating environment that includes other nucleotides, water molecules and sodium ions during the process of U80 conformational switch. It was found that hydrogen bonds between base pairs, bases and surrounding water molecules, as well as π-interactions between bases are involved in the process.

• Keywords: modeliranje; nekovalentne interakcije; kvercetin; U6; RNA
• Keywords (english): modelling; non-covalent interactions; quercetin; U6; RNA
• Language: croatian
• URN:NBN: urn:nbn:hr:163:460350
• Study programme: Title: Pharmacy; Study programme type: university; Study level: integrated undergraduate and graduate; Academic / professional title: magistar/magistra farmacije (magistar/magistra farmacije)
• Type of resource: Text
• File origin: Born digital
• Access conditions: Open access
• Created on: 2020-02-24 08:31:15