20.500.12556/DKUM-77539 Detekcija ohranjenih vod na medproteinskih površinah diplomsko delo univerzitetnega študijskega programa I. stopnje Identification of conserved waters on protein interfaces Študij ohranjenih vod je v sodobni farmacevtski kemiji ključnega pomena. Ne samo da ima voda pomembno vlogo v vseh bioloških procesih, temveč molekule vode ključno prispevajo pri interakcijah med proteini. Kristalne strukture kompleksov, pridobljene z visoko ločljivostjo iz različnih vendar homolognih proteinov, so pokazale, da so nekatere vode na medproteinski površini ohranjene med dvema homolognima kompleksoma. Ohranjene vode nastopajo pri tvorjenju vodikovih vezi, imajo strukturno vlogo pri makromolekulah, kjer tvorijo kompleksne mreže molekul, ki stabilizirajo njihovo strukturo. V diplomski nalogi smo s pomočjo računalniškega programa PyMOL identificirali medproteinsko površino sistema programirane celične smrt hPD-1 in njenega liganda hPD-L1 ter sistema beta rastnega faktorja Tgf-β3 in receptorja Tgf-β tipa II. Na tej medproteinski površini smo nato z orodjem ProBis H2O identificirali ohranjene molekule vode. Za vsako molekulo vode smo analizirali njene interakcije z aminokislinskimi ostanki in z ostalo medproteinsko površino. Ugotovili smo, da nekatere od teh ohranjenih molekul vod igrajo pomembno vlogo pri interakcijah med proteini ter so ključnega pomena za nujno komplementarnost. Poleg tega smo izračunali tudi energijo medproteinske interakcije in analizirali, kako vode vplivajo na celotno površino in vezavo med proteinoma. Rezultati analize nam lahko pomagajo pri predvidevanju interakcij med proteini, karakterizaciji vezavnih mest ter optimizaciji in razvoju zdravil The study of conserved waters is crucial in modern pharmaceutical chemistry. Not only that water plays an important role in all biological processes, but water molecules play a key role in protein-protein interactions (PPI) as well. The high-resolution crystal structures from different homologous proteins show that certain waters on the protein interfaces retain their location. They are named conserved waters and paticipate in the formation of key hydrogen bonds, play a structural role and stabilize macromolecular structures. In this thesis, we used computer programme PyMOL to identify the protein interface of human programmed death-1 (PD-1)-PD-L1 complex and transforming growth factor beta Tgf-β3 and TGF-beta Type II receptor complex. Conserved water molecules were then identified on these protein interfaces using ProBis H2O software. For each water molecule, its interactions at the protein interface were analysed. We found that conserved water molecules play an important role in protein-protein interactions (PPI) and are crucial for the interface complementarity. In addition, we also calculated the energy of the interface interactions and confirmed that all of the identified conserved waters contribute favourably to the interface binding. The results of this work can help us to predict protein-protein interactions (PPI), characterize binding sites, as well as to optimize and develop novel drugs. ohranjene vode medproteinska površina vodikova vez hidrofobni učinek ProBiS H2O conserved waters protein-protein interface hydrogen bond hydrophobic effect ProBiS H2O true true false [I. Masten] Slovenski jezik Angleški jezik Diplomsko delo/naloga 2020-09-02 21:47:02 2020-10-08 12:55:53 2022-08-09 15:42:14 2020-10-25 03:11:18 2020 0 Maribor 0 Maribor X, 40 str. 0000-00-00 NiDoloceno NiDoloceno NiDoloceno 0000-00-00 0000-00-00 0000-00-00 577.112(043.2) 33831939 URN:SI:UM:DK:49HORUC7 UN_Masten_Ines_2020.pdf UN_Masten_Ines_2020.pdf 1 CD1194E704CF65FC96A83D628537D95B 952787080dd19288951b978278fe5c4537b4c4c1e7f2a3f86a304878ed9a982d d3ea272d-7c11-11eb-bb7a-00155d0001ca 20.500.12556/dkum/660a1809-099e-425b-a360-2afdf164c92e https://dk.um.si/Dokument.php?lang=slv&id=145792 Fakulteta za kemijo in kemijsko tehnologijo 0 0 0