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Computer modeling of SARS-CoV-2 protease inhibition
Hanák, Martin ; Barvík, Ivan (advisor) ; Pospíšil, Miroslav (referee)
This work deals with various methods of computing free energy using molecular dy- namics simulations to study the inhibition of biological macromolecules and to identify potential drugs. Specifically, the possibility of using non-equilibrium methods based on Jarzynski's equality and Crooks fluctuation theorem was explored. The methods used were tested on simple systems of amino acids and a complex of ether crown with potas- sium. Subsequently, the tested methods were applied to complexes of adamantanes with cyclodextrins and especially to the inhibition of the main protease of SARS-CoV-2 Mpro. 1
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Computational Modeling of Membrane Proteins
Šimko, Pavol ; Barvík, Ivan (advisor) ; Pospíšil, Miroslav (referee)
The present work deals with the application of steered molecular dynamics simulations on medically interesting biomolecular systems. At first, methods for determi- ning the free energy profile were tested on the (Ala)10 model system. Then we focused on determining the free energy profile for binding of a ligand to the adenosine A2A GPC receptor. We further studied the free energy profile associated with ion passage through the Gramicidin A ion channel. Finally, we applied this methodology to the TRPM2 ion channel. 1
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Molecular dynamics simulations of biomolecular complexes consisting of proteins and nucleic acids
Melcr, Josef ; Barvík, Ivan (advisor) ; Bok, Jiří (referee)
Literature search on the Elongation factor Tu (EF-Tu), which is involved in the process of translation of genetic information, was performed. Further, computational methods as molecular dynamics (MD) and Monte Carlo (MC) were studied. Then, computer programs for MD and MC simulations of a Lennard-Jones gas were developed. MD simulations were further applied to EF-Tu using the NAMD and ACEMD software packages. Multiprocessor PC clusters and programmable NVIDIA GPUs were used. MD simulations of EF-Tu uncovered binding of monovalent ions in nearby of the EF-Tu active site. The impact of Na$^+$ binding on evolutionarily conserved residues (His85, Val20, Ile61, Asp21, Tyr47, Asp87, etc.) was studied in detail.
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Molecular dynamics simulations of complexes consisting of proteins and nucleic acids
Šmít, Daniel ; Barvík, Ivan (advisor) ; Štěpánek, Petr (referee)
Na/ev pracc: Molekularne-dynamicke simulace komplcxu sestavajicich z nukleovyeh kyselin a proleinu Autor: Daniel Snu't Katedra (ustav): Fy/ikalni ustav UK Vedouci hukalafskc prace: RNDr. Ivan Barvik. Ph.D. e-mail vedoueiho: iharvikiY/'karlov.mff.euni.c/ Abstrakt: Prace od /akladu se/namujc s biochemickymi principy. struklurou nukleovych kysclin a aminokyselin, stavbou proleinu a mechanismem jejich synte/y. /vlastni zfetel jc kladen na /pusoby replikacc nukleovych kysclin ruznyeh viru a na mo/nosli lerapie zalozene na interferenci s toulo replikaci. Dale jsou nastmeny i jine moderni melody lerapie spoci'vajici v modulaci imunity ei vyu/ili RNA interference. Struklura viru IICV je podrobne popsana. Replikacni en7\'in viru. IK'V RNA depcndenlni KNA polymcra/a, je podrt>bne popsan spolu s pfedpokladunym prubehcm jelut iniciace a poKmeracni akiiviiy. Dale jsou popsans /aklady molekularne dynamickych (Ml)) simulaci. ktere jsou v ranici bakalafske prace denionstrovany na jednoduchem modelovem systemu argonoveho clusteru. V druhe polovinc prace jsou provedeny MD simulace inhihice IK'V RclRp prostrednictvim lalek PMIXi, PMPG a IIPMPG. Struklura a stabilita komplexu je dctailnc analy/ovana na atomarni urovni. Klicova slova: molekularni dynamika. nuklcove kyseliny, IICV. IIPMIJ(j Title: Molecular dynamics simulations...
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MD simulations of complexes between nucleic acids and RNase H
Bartek, Tomáš ; Barvík, Ivan (advisor) ; Burda, Jaroslav (referee)
The aim of this diploma thesis was to study interactions between human Rase H enzyme and a natural and modified substrate using molecular dynamics simulations (altogether 9 MD runs ere produced). Conformational preferences of internucleotide linkages (undergoing contacts with the RNase H enzyme) were studied using several versions of the AMBER force field. Either one or two copies of RNase H were included into the simulated system. As the most important DNA-binding residues were recognized Trp93 and Ser101 in the first DNA binding site and Thr49 and Arg47 in the second DNA binding site. Further, the AMBER force field was re-parameterized slightly using ab initio calculations to produce force constants for the modified phosphonate internucleotide linkage. Biologically active version of the modified internucleotide linkage C3-O3-P-C-O5-C5 was able to bind Arg47 using two hydrogen bonds within the 10 ns MD run (even more effciently than in the case of MD runs with natural internucleotide linkages). On the other hand, the biologically inactive C3-O3-C-P-O5-C5 internucleotide linkage lose contacts with Arg47 quickly.
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Molecular dynamics simulations of membrane proteins
Španěl, David ; Barvík, Ivan (advisor) ; Bok, Jiří (referee)
Basic facts about the structure of biomolecules and algorithms applied in molecular dynamics (MD) simulations were recapitulated in the theoretical part of this thesis. A program for MD simulations of a periodic box with water molecules represented by various models (SPC, TIPS, TIP3P) was developed for active mastery of basic algorithms applied in MD simulations. MD simulation methodology was subsequently applied to the structure of the membrane protein A2AGPCR anchored in the phospholipid bilayer and surrounded by water molecules (approx. 120,000 atoms altogether). The purpose of these MD simulations was to compare binding of the natural agonist (adenosine) and its synthetic analog NECA into the binding pocket situated on the extracellular side of A2AGPCR. For these MD simulations were used software package NAMD and computer cluster Gram (in which each node is equipped with 16 CPU cores and 4 GPU) in supercomputing MetaCentrum. Powered by TCPDF (www.tcpdf.org)
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Molecular dynamics simulations of biomolecules
Naništa, Ján ; Barvík, Ivan (advisor) ; Bok, Jiří (referee)
This study deals with classical molecular dynamics simulations of time evolution of a biomolecular system. The simulated system consists of the D3 GPCR membrane receptor for dopamine surrounded by a cell membrane and covered with water molecules and ions. The aim was to analyze the ability of Eticlopride to bind into the active site of the GPCR receptor.
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