Primerjava proteomov glavnih predstavnikov virusov iz družine Filoviridae in identifikacija potencialnih vezavnih mest za načrtovanje ligandov

magistrsko delo

Katja Gole (Avtor), Marko Jukič (Mentor), Urban Bren (Komentor)

Povzetek

Virus Ebola Zaire (EBOV) in virus Marburg Marburg (MARV) sta glavna predstavnika družine Filoviridae, ki pri ljudeh povzročata hudo virusno hemoragično mrzlico, s stopnjo smrtnosti do 90 %. Kljub temu je zaradi le občasnih izbruhov bolezni, ki jih ni možno predvideti, razvoj zdravil okrnjen in se izvaja predvsem v akademskih krogih. V magistrskem delu smo preverjali podobnost virusnih proteomov in vezavnih mest z namenom, da bi v prihodnje bilo možno načrtovati učinkovine, ki bi se lahko vezale na terapevtske tarče obeh virusov. EBOV in MARV kodirata enakih sedem proteinov, in sicer NP, VP35, VP40, GP, VP30, VP24 in L protein, ki imajo glede na informacije, ki smo jih pridobili s pomočjo podatkovnih zbirk UniProt in PDB, podobne funkcije in zgradbo. Podobnost proteomov smo potrdili še z BLAST analizo aminokislinskih sekvenc med posameznimi proteini obeh virusov, pri čemer se podobnost proteinov giblje med 44 in 55 %, oziroma 68 % v 1. delu sekvence L proteinov. S programom ProBiS smo glede na primerjavo z že znanimi strukturami podobnih proteinov določili potencialna vezavna mesta in pripadajoče potencialne ligande. Vezavna mesta smo opisali in jih primerjali s pomočjo superpozicije proteinov obeh virusov. Kot rezultat smo pridobili tri pare podobnih vezavnih mest, ki se kljub podobnosti razlikujejo v posameznih aminokislinah, kar smo dokazali z BLAST primerjavo. S PLIP analizo smo pokazali, da aminokislinski ostanki v vezavnem mestu posameznega virusa tvorijo podobne interakcije z enakimi ligandi in da s tem obstaja možnost načrtovanja terapevtikov, ki bi se hkrati vezali na tarče EBOV in MARV.

Ključne besede

Ebola;Marburg;BLAST;vezavna mesta;ProBiS;načrtovanje ligandov;magistrske naloge;

Podatki

Jezik:	Slovenski jezik
Leto izida:	2024
Tipologija:	2.09 - Magistrsko delo
Organizacija:	UM FKKT - Fakulteta za kemijo in kemijsko tehnologijo
Založnik:	[K. Gole]
UDK:	547.964:615.281.8(043.2)
COBISS:	204115971
Št. ogledov:	82
Št. prenosov:	8
Ocena:	0 (0 glasov)
Metapodatki:

Ostali podatki

Sekundarni jezik:	Angleški jezik
Sekundarni naslov:	Comparison of proteomes of the main representatives of viruses from the Filoviridae family and identification of potential binding sites for ligand design
Sekundarni povzetek:	Ebola Zaire virus (EBOV) and Marburg Marburg virus (MARV) are the main representatives of the Filoviridae family that cause severe viral hemorrhagic fever in humans, with a fatality rate of up to 90 %. Nevertheless, due to only occasional outbreaks of the disease, which cannot be predicted, drug development is curtailed and is carried out mainly in academic circles. In the master's thesis, we checked the similarity of viral proteomes and binding sites with the aim that in the future it would be possible to design active substances that could bind to the therapeutic targets of both viruses. EBOV and MARV encode the same seven proteins, namely NP, VP35, VP40, GP, VP30, VP24, and L protein, which have similar functions and structures according to information obtained from UniProt and PDB databases. The similarity of the proteomes was also confirmed by BLAST analysis of the amino-acid sequences between the individual proteins of the two viruses, whereby the protein similarity varies between 44 and 55%, and even 68% in the 1st part of the L protein sequence. Using the ProBiS program, we determined potential binding sites and corresponding potential ligands based on a comparison with the already known structures of similar proteins. The binding sites were described and compared using the superposition of the proteins of the two viruses. As a result, we obtained three pairs of similar binding sites, which, despite their similarity, differ in individual amino-acid residues, which we proved by BLAST comparison. With PLIP analysis, we have shown that amino-acid residues in the binding site of individual viruses form similar interactions with the same ligands and that there is, therefore, a possibility of designing therapeutics that would simultaneously bind to EBOV and MARV targets.
Sekundarne ključne besede:	Ebola;Marburg;BLAST;binding sites;ProBiS;ligand design;
Vrsta dela (COBISS):	Magistrsko delo/naloga
Komentar na gradivo:	Univ. v Mariboru, Fak. za kemijo in kemijsko tehnologijo
Strani:	1 spletni vir (1 datoteka PDF (XV, 108 f.))
ID:	24343673