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Identification of the Protein Tunnels Using Molecular Dynamics
Kohout, Petr ; Martínek, Tomáš (referee) ; Musil, Miloš (advisor)
This thesis focuses on the analysis of protein structures. The aim is to design Caver Web 2.0 -- a new version of the web application that integrates additional scientific tools and allows users to go through a complicated workflow to provide relevant results without the need for a deeper knowledge of the integrated tools. Everything will be delivered through a simple and interactive user interface. The application extends the original Caver Web 1.0 application with new features. Caver Web 1.0 is a web server suitable for identifying protein tunnels and channels for which it allows to run ligand transport analyses. The program is characterized by an intuitive and user-friendly interface with minimum required input from the user. The server is suitable for researchers without advanced bioinformatics or technical knowledge. Its current version is well established and highly used in the scientific community (35,000 completed calculations in two years of operation). The most significant limitation of the current version is the ability to analyze only static structure, which often provides an incomplete biological picture. Therefore, it was decided to extend the tool to calculate molecular dynamics to provide a comprehensive picture of protein structure changes.
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The study of the association behavior of the amphiphilic copolymers in solutions containing low molar compounds by means of computer simulations.
Šindelka, Karel ; Limpouchová, Zuzana (advisor) ; Slavíček, Petr (referee) ; Vondrášek, Jiří (referee)
Title: The study of the association behaviour of the amphiphilic copolymers in solutions containing low molar compounds by means of computer simulations. Author: Mgr. Karel Šindelka Department: Faculty of Science, Charles University Supervisor: Doc. Ing. Zuzana Limpouchová, Csc. Abstract This doctoral thesis focuses on the study of electrostatic self- and co-assembly in complex polymer solutions containing polyelectrolyte (PE) block copolymers together with surfactants, neutral homopolymers, or oppositely charged PEs using the dissipative particle dynamics (DPD). It was shown that the electro- static self-assembly depends not only on the cooperative interactions of oppo- sitely charged PE chains, but also on the amphiphilicity of PE species or on the polymer block compatibility, among other properties. PEs with incompatible blocks create well-defined core-shell structures, while large ill-defined crew-cut aggregates form from PEs with compatible blocks In non-stoichiometric mixtures of PEs with incompatible blocks, co-assembled nanoparticles are smaller than in stoichiometric mixtures and are charged. The destabilization of larger aggregates depends on how the PE charge surplus is introduced: the effect is strongest when the density of the surplus PE charge on the PE chains is increased and weakest when the...
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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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Molecules in Cell Membranes
Timr, Štěpán ; Jungwirth, Pavel (advisor) ; Böckman, Rainer (referee) ; Ettrich, Rüdiger (referee)
Biological membranes are actively involved in a multitude of processes in living cells; therefore, a detailed characterization of their structure, dynamics, and function is essential for an understanding of living organisms at the molecular level. In this work, we made use of the high spatial and temporal resolution offered by computer simulations to investigate the behavior of several molecular species which associate with cellular membranes. Using a combination of classical molecular dynamics simulations and ab initio electronic structure calculations, we were able to characterize nonlinear optical properties of membrane- embedded fluorescent probes and thus contribute to establishing two-photon polarization microscopy as a tool of structural biology. Moreover, our molecular dynamics simulations provided an atomistic picture of the reversible membrane binding of recoverin, a neuronal calcium-sensing protein involved in vision adaptation, and they also yielded an important insight into the mechanism of its calcium-induced myristoyl switch. In addition, we examined the biological role of cholesterol oxidation and compared two methods of representing transmembrane voltage in molecular dynamics simulations.
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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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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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Design, parameterization and verification of a coarse-grained model of DNA
Dršata, Tomáš ; Lankaš, Filip (advisor) ; Jurečka, Petr (referee)
Structure and mechanical properties of DNA play a key role in its biological functioning. A lot of well-established conclusions about the DNA structure and its sequence-dependent variabil- ity came from various experimental and computational studies of the Dickerson-Drew dodecamer (DD), a prototypic B-DNA molecule of the sequence (5')CGCGAATTCGCG(3'). In this study we present a detailed analysis of structural and mechan- ical properties of DD based on extensive atomistic molecular dynamics (MD) simulations with explicit representation of wa- ter and ionic environment. We analyze three simulated systems covering different ionic conditions and water models. Two MD trajectories are reported for the first time, one of them being 2.4 µs long. An extensive comparsion with one recent NMR struc- ture and four recent X-ray structures is made. It is found that the end basepairs can adopt two different pairing motifs dur- ing the simulation: the canonical Watson-Crick pair or a non- canonical trans Watson-Crick/Sugar Edge pair. These states can significantly influence the structure of DD even at the third step from the end. A clear relationship is found between the BI/BII backbone substates and the basepair step conformation. A model of rigid bases is used to study mechanical properties of the DNA. The non-local...
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Molekulové simulace nukleace ledu
Pluhařová, Eva ; Jungwirth, Pavel (advisor) ; Kolafa, Jiří (referee)
Title: Molecular simulations of ice nucleation Author: Eva Pluhařová Department: Department of Physical and Macromolecular Chemistry Faculty of Science UK Advisor: doc. Mgr. Pavel Jungwirth, DSc., IOCB AS CR, v.v.i. Advisor's e-mail address: pavel.jungwirth@uochb.cas.cz Abstract: By means of molecular dynamics simulations we have systematically investigated homogeneous ice nucleation in neat and surface contaminated water. As models of the adsorbates we have assumed pentanol and pentanoic acid. In neat water nucleation preferentially starts in the subsurface region, which accommodates better than the bulk the volume increase associated with freezing. Homogeneous ice nucleation is affected more by alcohol than by acid. Water slabs covered by a disordered layer of pentanol exhibit negligible preference for subsurface nucleation and longer nucleation times in comparison with neat water, while nucleation times are almost unaffected by the presence of pentanoic acid and the subsurface preference is only slightly decreased. We tried to rationalize the differences between the effects of different compounds by their ability to orient water molecules and to change their mobility. The fact that adsorbates differ in the influence on homogeneous ice nucleation has important implications for the microphysics of...
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Development and applications of molecular dynamics for chiral systems
Kessler, Jiří ; Bouř, Petr (advisor) ; Fanfrlík, Jindřich (referee)
The Thesis deals with MD simulations of solutions of chiral solutes in chiral solvents. These solutions consist of 2,2,2-trifluoro-1-phenylethanol, 1-phenylethanol and 1-phenyl- ethanamine.The differences in NMR properties between different combnations of solvent and solute absolute configuration were modeled. Indeed, differences in radial distribution functions and conformer abundances of solute calculated by the WHAM method were found. These results correlated with experimental differences in NMR shifts. Additionally, a method of cluster preselection was developed. It significantly decreased the amount of clusters needed for computations of NMR shieldings and hence the computer time. Keywords: chirality, molecular dynamic, nuclear magnetic resonance
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