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QM/MM výpočty a klasické molekulárně-dynamické simulace biomolekul
Melcr, Josef ; Barvík, Ivan (advisor) ; Rulíšek, Lubomír (referee)
Systematic calculations were performed to uncover the free energy surfaces for hydrolytic reactions of methyl-diphosphate (in vacuum and implicit solvents) and GTP in EF-Tu active site. Density functional theory and ONIOM extrapolative QM/MM scheme were adopted for the assay. In accordance with experiments, the catalytic effect of the sodium cation was mild. It changes the conformation of GTP attracting its negatively charged oxygen atoms. hydrolýze GTP. The Na+ also equilibrates the charges of all phosphate groups of the GTP mostly by transferring electrons from gamma to beta-phosphate group, which is characteristic for the intermediate states during the hydrolytic reaction.
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Molecular dynamics study of admixture influence on structural properties and stability of fatty acid Langmuir monolayers
Kubániová, Denisa ; Roeselová, Martina (advisor) ; Barvík, Ivan (referee)
Using the classical molecular dynamics simulations, the interfacial partitioning of selected aromatic species, namely benzoic acid and neutral and zwitterionic form of L-phenylalanine, was studied in the three slab systems: a) aqueous organics solution, b) palmitic acid monolayer in tilted condensed phase at aqueous organics solution and c) palmitic acid monolayer in tilted condensed - 2D gas phase coexistence at aqueous organics solution. The surface activity and the tendency to aggregate in particular at the air- aqueous and palmitic acid-aqueous interface was confirmed for all of the investigated aromatic species. The results of the simulation performed for the system of palmitic acid monolayer at benzoic acid solution were compared with the literature results of a similar simulation that employed a different parametrization. The comparison showed that the behaviour of the aromatic species at the fatty acid monolayer-aqueous interface strongly depends on the force field. The structural properties of the palmitic acid Langmuir monolayers were evaluated by means of the chain tilt angle and the headgroup region dihedral angle distributions analysis depending on the surface film density and the adsorbed aromatic species. The simulations mimicking the isothermal compression of the mixed monolayer in the...
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Molecular dynamics simulations of the muscarinic receptor
Cajzl, Radim ; Barvík, Ivan (advisor) ; Pospíšil, Miroslav (referee)
Title: Molecular dynamics simulations of the muscarinic receptor Author: Radim Cajzl Department: Institute of Physics of Charles University Supervisor: RNDr. Ivan Barvík, Ph.D., Division of Biomolecular Physics Abstract: This thesis is devoted to molecular dynamics simulations of the mus- carinic M2 receptor placed in a phospholipidic membrane. Basic algorithms of molecular dynamics are described and applied on a simple model of rare gases. Relations for calculation of binding free energies are derived. Several tricks for sa- ving up computational time are presented. Next part contains a brief description of proteins and cellular membranes, structure and biological relevance of musca- rinic receptors and known crystal structures of the muscarinic M2 receptor. The chapter with results contains detailed description of calculations of bin- ding free energy differences for several ligands bound to the muscarinic M2 recep- tor. Obtained values match the experimental ones. Dynamics of the muscarinic M2 receptor was also studied yielding a direction for future studies of the acti- vation mechanism. Short discussion on application of obtained results in rational drug design can be found in the Conclusion chapter. Keywords: molecular dynamics, membrane proteins, free energy perturbation, muscarinic receptor,...
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Computer modelling of biomolecules - potential chemoterapeutics
Maláč, Kamil ; Barvík, Ivan (advisor) ; Jungwirth, Pavel (referee) ; Ettrich, Rüdiger (referee)
Classical molecular dynamics simulations were applied on complexes of RNA-dependent RNA-polymerase, Ribonuclease H, Argonaute and Ribonuclease L with chemically modified nucleic acids, which are studied as potential chemotherapeutic agents. Powerful graphics processing units, through which these molecular dynamics simulations were performed, enabled to acquire trajectory length from hundreds of nanoseconds to one microsecond. Molecular dynamics simulations allowed capture differences in binding of various modified nucleic acids to the above mentioned enzymes. These identified differences fitted well with experimental results. It opens the door for rational design of the structure of potential chemotherapeutic agents based on chemically modified nucleic acids.
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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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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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Molecular dynamics simulations of complexes consisting of proteins and nucleic acids
Hammer, Jiří ; Barvík, Ivan (advisor) ; Obšil, Tomáš (referee)
The goal of this diploma thesis was to study interactions of Argonaute (Ago) protein in a complex with nucleic acids. Based on the available crystal structures of full length Argonaute (from A. aeolicus, Aa-Ago) and/or its domains (human PAZ domain, Hs-PAZ), twelve different simulations were computed. Two initial simulations used model of Aa-Ago with either a duplex of DNA/RNA or RNA/RNA. Major difference was in behavior of the PAZ domain (especially its arginine residues), which tolerated the guide DNA in one simulation, but was disturbing the RNA guide strand in the second. Such an interaction could serve as a mechanism of the substrate recognition. In additional simulations (3-9) employing the Hs-PAZ domain, where no disturbance was found in the DNA/RNA hetero-duplex. Different arrangements of the active site geometry as well as empirical parameterizations of Mg2+ ion were probed and analyzed. The DD-catalytic motif plus D683 in Aa-Ago (equivalent to H807 in human Argonaute2) was observed to coordinate the Mg2+ ion in one and two metal ion dependent catalysis models. Highly conserved R570 and E578 created mutual hydrogen bonds and hence stabilized the active site. To make the cleavage irreversible, a role for the first (unpaired) nucleotide from 5'-end of the guide strand was suggested. It lies in a...
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