|
|
Covalent geometry of nucleic acids
Schramlová, Barbora ; Černý, Jiří (advisor) ; Dohnálek, Jan (referee)
IV Abstract Nucleic acids (NA) are substances that play a fundamental role in all living organisms. They store genetic information and control the process of protein synthesis. These macromolecules are composed of chains of nucleotides. According to the type of sugar in the nucleotides, nucleic acids are divided into DNA (Deoxyribonucleic acid) and RNA (Ribonucleic acid). Nucleotide sequences also determine the spatial conformations of nucleic acids. At the level of dinucleotides, conformations are described by classes of dinucleotide conformers - NtC. To study nucleic acids, it is crucial to determine their spatial arrangement. The most common method of three-dimensional observations is X-ray crystallography, which uses the interaction of X-rays with the electron cloud of atoms in the crystal. The result is crystallographic data, which further goes through the process of refinement and validation. One of the essential requirements for reliable refinement and validation are stereochemical standards. These are vocabularies that characterize specific bond lengths, bond angles, torsion angles, planes, and chirality. These parameters were last updated in 2020, but their quality still needs to be improved. This work focuses on the detailed characterization and description of the covalent geometry of nucleic...
|
|
|
HIV - 1 Protease: Insights into Drug Resistance Development
Grantz Šašková, Klára ; Konvalinka, Jan (advisor) ; Forstová, Jitka (referee) ; Dohnálek, Jan (referee) ; Schiffer, Celia (referee)
Amino acid changes within HIV protease or its substrate that decrease the susceptibility to protease inhibitors represent a highly complex issue still not yet fully understood. Various mechanisms by which this often complicated pattern of mutations influence drug binding needs to be analyzed on a molecular level by a series of methods including experiments with recombinant viruses, biochemical enzyme analysis, structural and thermodynamical studies or molecular dynamics. Each result may help to complete the overall picture of protease inhibitor resistance evolution and therefore contribute to the design of more powerful 3rd generation HIV/AIDS drugs. This thesis presents several analyses of HIV resistance development on molecular level. We have focused on the nelfinavir resistance pathway, lopinavir mutation score, emergence of amino acid insertions in HIV protease gene and their contribution to protease inhibitor resistance and finally we analyzed a highly mutated protease species isolated from patients failing darunavir therapy. Since we are able to accomplish a wide combination of techniques, we could explain and put together some pieces of viral evolution considering the final steps of HIV life cycle and also provide knowledge necessary for novel inhibitor design. Aims of the Project There were...
|
|
|
Nucleic Acid Geometry Standards
Schramlová, Barbora ; Černý, Jiří (advisor) ; Dohnálek, Jan (referee)
IV Abstract Nucleic acids (NA) are biochemical macromolecular substances essential for all living organisms - their function is to store genetic information and control the process of protein biosynthesis. Nucleic acids are composed of polynucleotide chains. According to the composition of these, we distinguish two basic types of nucleic acids: DNA (Deoxyribonucleic Acid) and RNA (Ribonucleic Acid). Based on the internal nucleotide sequence and external interactions, these chains are formed into different spatial conformations. At the dinucleotide level, these conformations are described and classified by so-called classes of dinucleotide conformers - NtC. The X-ray crystallography method has been used for over 50 years to reveal the three- dimensional structures of biological macromolecules. The principle of this is the interaction of X-rays with the electron cloud of atoms in the crystal. Atomic positions are then determined based on the calculated electron density. However, with the resolution available for most macromolecular crystals, these crystallographic data are not sufficient to derive a chemically acceptable structure, so stereochemical restraints apply. Stereochemical restraints are dictionaries describing specific bond lengths, bond angles, torsion angles, planes, and chirality. Using these...
|
|
|
Territorial decision-making processes
Dohnálek, Jan ; Svoboda, Petr (advisor) ; Vedral, Josef (referee)
Territorial Decision-Making Processes Abstract The thesis deals with the territorial decision-making from the perspective of the Act No. 183/2006 Coll., on Town and Country Planning and Building Code (Building Act), and provides the reader with the comprehensive, logical and structured overview of the different territorial decision-making processes. Chapter 1.1 defines terms Area, Developed Area, Area with Development Potential, Ground without Development Potential and Non-developed Area. In chapter 1.2 the territorial decision-making is placed into the structure of construction law, administrative law and public law. Attention is being given to spatial planning, its objectives, tasks and legal sources. In the rest of the chapter the planing materials, spatial development policy, planning documentation and planning measure on building ban and on redevelopment are briefly introduced. Chapters 2.1 to 2.7 are subsequently devoted to the territorial decision- making itself as the executive instrument of the spatial planning. After the initial acquaintance with the Territorial Decision-making term in chapter 2.1 the thesis identifies five relatively self- standing aspects in chapter 2.2 through which the territorial decision-making is further assessed. In this context chapter 2.3 deals with the territorial...
|
|
|
Structure Analysis of Plant Bifunctional Nuclease TBN1
Kovaľ, Tomáš ; Dohnálek, Jan (advisor) ; Brynda, Jiří (referee) ; Schneider, Bohdan (referee)
This work is dedicated to thorough structural analysis of plant bifunctional nuclease TBN1, the representative of plant nuclease I group. TBN1 along with homologous nucleases from this family plays an important role in plant cell life cycle and also shows considerable anticancerogenic effects. Two variants of TBN1 (wild type and N211D mutant) were studied. Properties of both variants in different solutions were analyzed. Both were successfully crystallized. Structures of both types of TBN1 were solved using X-ray diffraction. The phase problem was solved by Multi-wavelength anomalous dispersion using Zn2+ ions natively present in TBN1. Structural properties of TBN1 such as fold, active site composition, effect of glycosylation and surface electrostatic potential distribution were analyzed. Reaction mechanism of TBN1 was proposed on the basis of structural properties and comparisons with similar structures.
|
|
|
HIV - 1 Protease: Insights into Drug Resistance Development
Grantz Šašková, Klára ; Konvalinka, Jan (advisor) ; Forstová, Jitka (referee) ; Dohnálek, Jan (referee) ; Schiffer, Celia (referee)
Amino acid changes within HIV protease or its substrate that decrease the susceptibility to protease inhibitors represent a highly complex issue still not yet fully understood. Various mechanisms by which this often complicated pattern of mutations influence drug binding needs to be analyzed on a molecular level by a series of methods including experiments with recombinant viruses, biochemical enzyme analysis, structural and thermodynamical studies or molecular dynamics. Each result may help to complete the overall picture of protease inhibitor resistance evolution and therefore contribute to the design of more powerful 3rd generation HIV/AIDS drugs. This thesis presents several analyses of HIV resistance development on molecular level. We have focused on the nelfinavir resistance pathway, lopinavir mutation score, emergence of amino acid insertions in HIV protease gene and their contribution to protease inhibitor resistance and finally we analyzed a highly mutated protease species isolated from patients failing darunavir therapy. Since we are able to accomplish a wide combination of techniques, we could explain and put together some pieces of viral evolution considering the final steps of HIV life cycle and also provide knowledge necessary for novel inhibitor design. Aims of the Project There were...
|
|
|
Traktory Deutz - Fahr
Dohnálek, Jan
Dohnálek, J. Tractor Deutz-Fahr. Bachelor thesis. MENDEL UNIVERSITY Brno Faculty of Agronomy, 2015. Bachelor thesis deals with tractors particular brand DEUTZ-FAHR. The paper analyzes the partially history of the brand but also the current state of the domestic market. There are also information about the exclusive importer, its services and service center. In the last part contains an analysis of a particular tractor DEUTZ-FAHR Agrotron TTV 7, which is divided into three parts: engine, transmission and hydraulic, control part.
|
|
|
Valuation of Structured Products
Dohnálek, Jan ; Brada, Jaroslav (advisor) ; Kováč, Michal (referee)
The objective of the thesis is to acquaint readers with field of structured product valuation. It is a relatively complex issue which is, however, based on general valuation foundations. The opening chapter is dedicated to these general fundamentals of valuation. Emphasis is placed mainly on present value principle, a specific variant of comparison, and its related aspects. The second section describes key elements of structured product valuation. Greater part of this chapter is devoted to the Monte Carlo simulation, the most employed tool in valuation of these products in practice. An important part of Monte Carlo simulation is an option spread, which arises as by-product of the simulation and reflects value of an option contained in the evaluated instrument. Third chapter is focused on interest rate and prepayment models. Level of prepayment is dependent on interest rates development which both are the most critical factors that affect value of structured products. Description of models includes theoretical and mathematical formulation as well as mentioning their advantages and disadvantages. Valuation model is illustrated in the last part, which is demonstrated on valuation of hypothetical structured products example. Based on the model, the development of cash flows from underlying asset portfolio is forecasted which in turn determines the value of evaluated instruments. The final section deals with advantages of structured products and, hence, why banks and other institutions use them in practice.
|
|
| |
guest ::
RSS feed.