20.500.12556/RUL-164786 A method for construction and optimization of lipid nanodisks for molecular dynamics simulations Metoda za konstrukcijo in optimizacijo lipidnih nanodiskov za simulacije molekularne dinamike Lipid nanodisks are lipid bilayer structures stabilized by a belt of alipoproteins. They play a critical role in studying membrane proteins and developing drug delivery systems. Mimetic peptides offer a simplified yet effective alternative to full-length apolipoproteins in stabilizing these nanodisks, providing a platform for understanding lipid-protein interactions and exploring therapeutic applications. The objective of this thesis was to develop, implement, and test a computational protocol for constructing and simulating nanodisks composed of lipid bilayers and stabilized by mimetic peptides, using molecular dynamics all-atom simula tions with the charmm36m forcefield. Five all-atom simulations were conducted to study the structural dynamics of nanodisks formed by 14A peptide dimers and DMPClipids. Anadditional simulation was done by replacing DMPC with POPC and cholesterol, to study the effect of different lipids on nanodisk properties. The presence of cholesterol in the POPC system led to slower stabilization and less shrinkage, likely due to increased membrane rigidity. Coarse-grained simulations using the Martini 3 forcefield were explored for their potential to accelerate sim ulation times. Construction was successful, but the coarse-grain models failed to maintain structural integrity during production runs, indicating that current coarse-grain models may not accurately represent interactions between peptide dimers. While coarse-grain simulations offer the potential for significant accelera tion of the simulation speed, further refinement of the forcefield and stabilization strategies are necessary for reliable nanodisk modeling. Lipoproteini so nanostrukture, bistvene za transport lipidov v krvnem obtoku zaradi hidrofobnosti lipidov. Sestavljeni so iz apolipoproteinov in razliˇ cnih lipi dov, vkljuˇcno s holesterolom in trigliceridi. Med ˇstirimi glavnimi vrstami lipopro teinov—HDL, LDL, VLDL in IDL—je HDL najbolj znan po svoji sestavi in funkciji [1]. HDL, ki je sestavljen predvsem apolipoproteina A1 (Apo-AI) in fosfolipidov, je kljuˇcen za reverzni transport holesterola (angl. reverse cholesterol transport), kar zmanjˇsuje aterosklerozo in tveganje za kardiovaskularne bolezni. nanodisks mimetic peptides molecular dynamics simulations all atom coarse-grain lipid bilayer Lipid-protein interactions apolipoproteins nanodiski mimetiˇcni peptidi simulacije molekularne di namike atomistiˇcno polje sil grobozrnato polje sil lipidni dvosloj interakcije lipid-protein apolipoproteini true false false Angleški jezik Slovenski jezik Magistrsko delo/naloga 2024-11-12 11:10:13 2024-11-12 11:10:21 2024-12-11 09:27:15 0000-00-00 00:00:00 2024 0 0 0000-00-00 NiDoloceno NiDoloceno NiDoloceno 0000-00-00 0000-00-00 0000-00-00 62754 218522371 Ivanus_Bor_-_Metoda_za_konstrukcijo_in_optimizacijo_lipidnih_nanodiskov_za_simulacije_molekularn.pdf Ivanus_Bor_-_Metoda_za_konstrukcijo_in_optimizacijo_lipidnih_nanodiskov_za_simulacije_molekularn.pdf 1 41367B3B2C813B0363891686D1411B42 2aa007e761d895dcb0f18edbbbe20a6a27ca5384a05d10762bd923bc24676bda fb5d1c9b-a0dd-11ef-b232-0050569b8976 https://repozitorij.uni-lj.si/Dokument.php?lang=slv&id=195469 Fakulteta za elektrotehniko 0 0 0