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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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Distribution of ions at surfaces of hydrated proteins
Heyda, Jan ; Barvík, Ivan (referee) ; Jungwirth, Pavel (advisor)
By means of molecular dynamics simulations we have systematically investigated the behavior of positively charged amino acids - arginine, lysine, and histidine in salt solutions. Salt always contained potassium cation and anions from the halide group. Both simple salts and binary salt solutions were investigated. Primarily, we have quantified the level of interaction of anions with amino acids. Also, the interaction sites were defined together with their role in cumulative interactions. The interaction was quantified by means of density maps, contacts, and cumulative sums with respect to individual parts of the amino acid. All simulations were done both with nonpolarizable and polarizable force fields. A significant difference in behavior between fluoride and other halides was observed in all cases. Fluoride preferentially interacted with the charged part of amino acids, while interactions of other halides were spread over the whole amino acid.
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