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Interaction preferences in protein - DNA complexes
Jakubec, Dávid ; Vondrášek, Jiří (advisor) ; Berka, Karel (referee)
Interaction preferences in protein - DNA complexes Dávid Jakubec Abstract Interactions of proteins with DNA lie at the basis of many fundamental bio- logical processes. Despite ongoing efforts, the rules governing the recognition of specific nucleic acid sequences have still not been universally elucidated. In this work, I attempt to explore the recognition process by splitting the intricate network of contacts at the protein - DNA interface into contribu- tions of individual amino acid - nucleotide pairs. These pairs are extracted from existing high-resolution structures of protein - DNA complexes and in- vestigated by bioinformatics and computational-chemistry based methods. Criteria of specificity based on the coupling of observed geometrical prefer- ences and the respective interaction energies are introduced. The application of these criteria is used to expand the library of amino acid - nucleotide pairs potentially significant for direct sequence recognition. Electrostatic poten- tial maps are calculated for individual nucleotides as well as for selected complexes to investigate the physical basis of the observed specificity. 1
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Identification of crystal packing contacts using a method for detection of protein-protein interaction sites
Mitková, Natália ; Hoksza, David (advisor) ; Jakubec, Dávid (referee)
One of the fundamental issues when obtaining the protein quaternary structures is to be able distinguish biological interfaces from crystal packing contacts. The existence of these false contacts is the consequence of the crystallographic method which is used for obtaining the tertiary and quaternary structure. Gaining knowledge of how proteins interact in 3D space is key to understanding their functions and offers the opportunity to apply the knowledge to inhibitor impact analysis, drug design, immunotherapy, or de novo protein design. Furthermore, this knowledge is an essential requirement when applying in silico approaches. The bachelor thesis is divided into two parts. The first part contains literature retrieval of existing methods addressing the problem of crystallographic contact detection together with relevant datasets for an objective evaluation. The second practical part is focused on the comparison of evaluations of the previously developed method for the protein-protein interface prediction, INSPiRE, and the EPPIC classifier. Key words: bioinformatics, crystal packing contact, crystallography, protein structure, protein- protein interactions
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Interactions of Proteins with Nucleic Acids: from Structure to Specificity
Jakubec, Dávid ; Vondrášek, Jiří (advisor) ; Šponer, Jiří (referee) ; Zagrovic, Bojan (referee)
Sequence-specific interactions between proteins and nucleic acids play an essential role in the cell biology. While several molecular mechanisms contributing to the binding speci- ficity have been identified empirically, no general protein-DNA recognition code has been described to date. In this thesis, I explore selected characteristics of protein-DNA inter- actions using computational methods. First, the pairwise interactions between the basic biomolecular building blocks-amino acids and nucleotides-are investigated. It is shown that several statistically enriched, biologically relevant interaction motifs correspond to the most energetically favorable configurations of the respective binding partners. In ad- dition, a relationship between the physico-chemical properties of the amino acid residues found at the protein-DNA interface and the local geometric features of the DNA helix is presented. Next, the applicability of molecular dynamics-based setups to the description of binding equilibria in protein-DNA systems is investigated. Discrepancies are observed between the description offered by the computer simulations and experimental results, as well as between the results obtained using two molecular mechanical force fields. Finally, the more general evolutionary aspects of protein organization...
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Interaction preferences in protein - DNA complexes
Jakubec, Dávid ; Vondrášek, Jiří (advisor) ; Berka, Karel (referee)
Interaction preferences in protein - DNA complexes Dávid Jakubec Abstract Interactions of proteins with DNA lie at the basis of many fundamental bio- logical processes. Despite ongoing efforts, the rules governing the recognition of specific nucleic acid sequences have still not been universally elucidated. In this work, I attempt to explore the recognition process by splitting the intricate network of contacts at the protein - DNA interface into contribu- tions of individual amino acid - nucleotide pairs. These pairs are extracted from existing high-resolution structures of protein - DNA complexes and in- vestigated by bioinformatics and computational-chemistry based methods. Criteria of specificity based on the coupling of observed geometrical prefer- ences and the respective interaction energies are introduced. The application of these criteria is used to expand the library of amino acid - nucleotide pairs potentially significant for direct sequence recognition. Electrostatic poten- tial maps are calculated for individual nucleotides as well as for selected complexes to investigate the physical basis of the observed specificity. 1
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The metabolism of amino acids in parasitic and anaerobic protists
Jakubec, Dávid ; Šuťák, Róbert (advisor) ; Hrdý, Ivan (referee)
Parasitic protists are the cause of countless pathological conditions and economic issues in many parts of the world. While being phylogenetically unrelated, they share many similarities in their approach to satisfying the essential needs. Unlike the much studied energy metabolism, amino acids utilisation pathways are rather unexplored areas. This review shows that in many cases, the parasitic life style has not had the same impact on the amino acid metabolism as it did on the energy metabolism of the protists, which is often severely reduced. Novel pathways have been found in many of the organisms in question, for the biosynthesis of amino acids deemed both essential and non-essential in humans. The arginine dihydrolase pathway found in Trichomonas and Giardia represents a complely new way of utilising the said amino acid. The metabolism of sulfur-containing amino acid has been a matter of intensive research for their non-proteogenic roles. Polyamines are organic nitrogenous compounds involved in many vital processes in the cells, including DNA replication and protein translation. The synthesis of polyamines and their derivatives is elucidated, as it is directly connected to the amino acid metabolism. Finally, the exploitation of the unique pathways described integrates the previous research with the aim...
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