Preverjanje napovedi heličnosti nestrukturiranih peptidov z eksperimentalnimi podatki

Purič, Samo (author), Lah, Jurij (mentor)

Za intrinzično nestrukturirane proteine (IDP-je, angl. »Intrinsically disordered proteins«) je značilna odsotnost enoznačno definirane 3D strukture. Njihova prostorska razporeditev se konstantno spreminja, pri določenih pogojih jih tako najdemo kot nabor različnih konformacijskih oblik, med katerimi, energijsko gledano, nobena zelo ne izstopa. Neurejena je lahko tudi samo regija oziroma domena proteina (IDR, angl. »Intrinsically disordered region«). Zardi svoje funkcionalnosti so IDP-ji udeleženi v signalizaciji, regulaciji in drugih celičnih procesih. Najbolj pogost strukturni element ki ga najdemo v IDP-jih (in tudi ostalih proteinih) je α-vijačnica. V tem diplomskem delu smo se osredotočili na algoritem AGADIR, ki se uporablja za napovedovanje vsebnosti α-vijačnice v monomernih peptidih na osnovi analize aminokislinskega zaporedja. Zbrali smo eksperimentalne podatke heličnosti peptidov IDP-jev pri katerih zaznamo težnjo po tvorjenju α-vijačnice iz literature (CD spektri) in te vrednosti primerjali z napovedjo algoritma AGADIR. Poleg tega smo opravili tudi analizo aminokislinskih zaporedij peptidov na podlagi lastnosti posameznih ak-ostankov in prešteli interakcije stranskih skupin ak-ostankov. Kot referenčen set podatkov smo uporabili sedem alaninskih peptidov, s pomočjo katerih je algoritem AGADIR umerjen. Na podlagi rezultatov lahko zaključimo, da AGADIR delež α-vijačnice v peptidih IDP-jev močno podceni, vendar pa z veliko večjo natančnostjo napove vsebnost α-vijačnice v alaninskih peptidih. Rezultati analize sekvenc in interakcij stranskih skupin kažejo na to, da AGADIR najverjetneje podceni ugodne energijske prispevke določenih interakcij, ki pripomorejo k stabilnosti α-vijačnice.

• Language: Slovenian
• Keywords: Intrinzično nestrukturiran protein, α-vijačnica, AGADIR
• Work type: Bachelor thesis/paper
• Typology: 2.11 - Undergraduate Thesis
• Organization: FKKT - Faculty of Chemistry and Chemical Technology
• Year: 2019
• PID: 20.500.12556/RUL-109872
• COBISS.SI-ID: 1538408899
• Publication date in RUL: 09.09.2019

PURIČ, Samo, 2019, Preverjanje napovedi heličnosti nestrukturiranih peptidov z eksperimentalnimi podatki [online]. Bachelor’s thesis. [Accessed 27 June 2025]. Retrieved from: https://repozitorij.uni-lj.si/IzpisGradiva.php?lang=eng&id=109872

Secondary language

• Language: English
• Title: /

Abstract

Intrinsically disordered proteins (IDPs) are proteins that lack a well-defined 3D structure. Their spatial arrangement is constantly changing, and we can only describe them (at a given temperature) as a set of distinct conformational shapes with very similar conformational energies. Apart from IDPs, intrinsically disordered regions (IDRs) are also very common. Because of their functional properties, IDPs are involved in many cellular processes such as signalization and regulation. The most common structural element that is found in IDPs is the α-helix. In this work, we focus on AGADIR, which is an algorithm for predicting α-helical content in monomeric peptides based on amino acid sequence. We gathered experimental data obtained with CD spectroscopy of peptides from IDPs with a significant helix propensity and compared the values with the ones determined by AGADIR. In addition, we also ran an analysis of amino acid sequences of the peptides used and the possible interactions between functional groups. As a reference set of data, we used seven alanine-based peptides. From the obtained data, we can see that AGADIR underestimates the α-helical content of peptides from IDPs, but on the other hand predicts the helical content of alanine-based peptides with a much higher degree of accuracy. The results of the sequence analysis suggest that AGADIR underscores the positive interactions between amino acid functional groups, responsible for stabilizing the α-helix.

• Keywords: Intrinsically disordered protein, α-helix, AGADIR