Mehanizmi interakcija ljudskog albumina i kaprilne kiseline in silico

master's thesis

• Title (english): In silico mechanisms of human albumins and caprylic acid interactions
• Author: Bruno Srezović Bijelić
• Mentor: Branimir Bertoša (mentor)
• Committee member: Branimir Bertoša (predsjednik povjerenstva)
• Committee member: Martina Šeruga Musić (član povjerenstva)
• Committee member: Kristian Vlahoviček (član povjerenstva)
• Committee member: Ivana Ivančić Baće (član povjerenstva)
• Granter: University of Zagreb; Faculty of Science; (Department of Biology); Zagreb
• Defense date and country: 2020-06-16, Croatia
• Scientific / art field, discipline and subdiscipline: NATURAL SCIENCES; Biology

Abstract

Taloženje kaprilnom kiselinom jedna je od metoda za uklanjanje nečistoća iz serumskih otopina. Naime, primijećeno je svojstvo kaprilne kiseline da pri određenim koncentracijama taloži albumin, dok imunoglobulini ostaju u otopini. Dosadašnja istraživanja ukazuju da dolazi do izravne interakcije između albumina i kaprilne kiseline u otopini, no mehanizam interakcije nije razjašnjen. Postojeći eksperimentalni podaci pokazuju da ova interakcija ima izraženu ovisnost o pH vrijednosti otopine. Cilj ovog diplomskog rada jest razjasniti mehanizam interakcije između kaprilne kiseline i ljudskog albumina koristeći računalne simulacije, u prvom redu simulacije molekularne dinamike. Korištenjem dostupnih kristalnih struktura ljudskog albumina izgrađeni su in slico modeli albumina i kaprilne kiseline na kojima su provedene simulacije molekularne dinamike. Simulacije su provedene na dvije pH vrijednosti, s protoniranim i deprotoniranim oblikom kaprilne kiseline, kako bi se razjasnili eksperimentalni podaci koji ukazuju na različite interakcije albumina i kaprilne kiseline pri različitim pH vrijednostima. Analizom rezultata simulacija istražene su nekovalentne interakcije u sustavima pri različitim pH vrijednostima otopine i njihov utjecaj na stabilnost albumina u prisutnosti kaprilne kiseline.

Abstract (english)

Protein precipitation mediated by caprylic acid is one of the methods used for removing impurities from serum. It was observed that certain concentrations of caprylic acid can cause precipitation of albumin while immunoglobulins remain dissolved. Although previous research points towards direct interactions occurring between albumin and caprylic acid in solution, the interaction mechanism has not been clarified. Existing experimental data indicate that this interaction has a pronounced pH dependence. The goal of this graduate thesis is to elucidate the molecular mechanism of interaction between caprylic acid and human albumin using computational simulations, particularly molecular dynamics simulations. Starting from the crystal structures of human albumin, in silico models of albumin and caprylic acid were prepared and subjected to molecular dynamics simulations. Simulations were conducted at two pH, using both protonated and deprotonated forms of caprylic acid. Analysis of simulations provided insight into dominant non-covalent interactions between the species in the systems at different pH values of the solution and their effect on the stability of albumin.

• Keywords: ljudski serumski albumin; kaprilna kiselina; molekularna dinamika; hidrofobne interakcije; vodikove veze
• Keywords (english): Human serum albumin; caprylic acid; molecular dynamics; hydrophobic interactions; hydrogen bonds
• Language: croatian
• URN:NBN: urn:nbn:hr:217:387658
• Study programme: Title: Molecular Biology; Study programme type: university; Study level: graduate; Academic / professional title: magistar/magistra molekularne biologije (magistar/magistra molekularne biologije)
• Type of resource: Text
• File origin: Born digital
• Access conditions: Open access
• Created on: 2020-07-13 06:29:00