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  • About
  • The Global ETD Search service is a free service for researchers to find electronic theses and dissertations. This service is provided by the Networked Digital Library of Theses and Dissertations.
    Our metadata is collected from universities around the world. If you manage a university/consortium/country archive and want to be added, details can be found on the NDLTD website.
1

Development of Proteochemometrics—A New Approach for Analysis of Protein-Ligand Interactions

Lapins, Maris January 2006 (has links)
<p>A new approach to analysis of protein-ligand interactions, termed proteochemometrics, has been developed. Contrary to traditional quantitative structure-activity relationship (QSAR) methods that aim to correlate a description of ligands to their interactions with one particular target protein, proteochemometrics considers many targets simultaneously.</p><p>Proteochemometrics thus analyzes the experimentally determined protein-ligand interaction activity data by correlating the data to a complex description of all interaction partners and; in a more general case even to interaction environment and assaying conditions, as well. In this way, a proteochemometric model analyzes an “interaction space,” from which only one cross-section would be contemplated by any one QSAR model.</p><p>Proteochemometric models reveal the physicochemical and structural properties that are essential for protein-ligand complementarity and determine specificity of molecular interactions. From a drug design perspective, models may find use in the design of drugs with improved selectivity and in the design of drugs for multiple targets, such as mutated proteins (e.g., drug resistant mutations of pathogens).</p><p>In this thesis, a general concept for creating of proteochemometric models and approaches for validation and interpretation of models are presented. Different types of physicochemical and structural description of ligands and macromolecules are evaluated; mathematical algorithms for proteochemometric modeling, in particular for analysis of large-scale data sets, are developed. Artificial chimeric proteins constructed according to principles of statistical design are used to derive high-resolution models for small classes of proteins.</p><p>The studies of this thesis use data sets comprising ligand interactions with several families of G protein-coupled receptors. The presented approach is, however, general and can be applied to study molecular recognition mechanisms of any class of drug targets.</p>
2

Development of Proteochemometrics—A New Approach for Analysis of Protein-Ligand Interactions

Lapins, Maris January 2006 (has links)
A new approach to analysis of protein-ligand interactions, termed proteochemometrics, has been developed. Contrary to traditional quantitative structure-activity relationship (QSAR) methods that aim to correlate a description of ligands to their interactions with one particular target protein, proteochemometrics considers many targets simultaneously. Proteochemometrics thus analyzes the experimentally determined protein-ligand interaction activity data by correlating the data to a complex description of all interaction partners and; in a more general case even to interaction environment and assaying conditions, as well. In this way, a proteochemometric model analyzes an “interaction space,” from which only one cross-section would be contemplated by any one QSAR model. Proteochemometric models reveal the physicochemical and structural properties that are essential for protein-ligand complementarity and determine specificity of molecular interactions. From a drug design perspective, models may find use in the design of drugs with improved selectivity and in the design of drugs for multiple targets, such as mutated proteins (e.g., drug resistant mutations of pathogens). In this thesis, a general concept for creating of proteochemometric models and approaches for validation and interpretation of models are presented. Different types of physicochemical and structural description of ligands and macromolecules are evaluated; mathematical algorithms for proteochemometric modeling, in particular for analysis of large-scale data sets, are developed. Artificial chimeric proteins constructed according to principles of statistical design are used to derive high-resolution models for small classes of proteins. The studies of this thesis use data sets comprising ligand interactions with several families of G protein-coupled receptors. The presented approach is, however, general and can be applied to study molecular recognition mechanisms of any class of drug targets.
3

Solid-phase reactions of N-carbamyliminium ions : from amino aldehydes to on-bead GPCR-screening /

Diness, Frederik. January 2006 (has links)
Ph.D.
4

ENHANCEMENT OF BRAIN MELANOCORTIN SIGNALING IN LEAN, ACTIVE RATS

Shukla, Charu 24 April 2014 (has links)
No description available.
5

Design, synthesis, and characterization of peptides and peptidomimetics for mouse melanocortin receptors

Joseph, Christine G. January 2004 (has links)
Thesis (Ph. D.)--University of Florida, 2004. / Typescript. Title from title page of source document. Document formatted into pages; contains 202 pages. Includes Vita. Includes bibliographical references.
6

Modeling the Interaction Space of Biological Macromolecules: A Proteochemometric Approach : Applications for Drug Discovery and Development

Kontijevskis, Aleksejs January 2008 (has links)
<p>Molecular interactions lie at the heart of myriad biological processes. Knowledge of molecular recognition processes and the ability to model and predict interactions of any biological molecule to any chemical compound are the key for better understanding of cell functions and discovery of more efficacious medicines.</p><p>This thesis presents contributions to the development of a novel chemo-bioinformatics approach called proteochemometrics; a general method for interaction space analysis of biological macromolecules and their ligands. In this work we explore proteochemometrics-based interaction models over broad groups of protein families, evaluate their validity and scope, and compare proteochemometrics to traditional modeling approaches.</p><p>Through the proteochemometric analysis of large interaction data sets of multiple retroviral proteases from various viral species we investigate complex mechanisms of drug resistance in HIV-1 and discover general physicochemical determinants of substrate cleavage efficiency and binding in retroviral proteases. We further demonstrate how global proteochemometric models can be used for design of protease inhibitors with broad activity on drug-resistant viral mutants, for monitoring drug resistance mechanisms in the physicochemical sense and prediction of potential HIV-1 evolution trajectories. We provide novel insights into the complexity of HIV-1 protease specificity by constructing a generalized IF-THEN rule model based on bioinformatics analysis of the largest set of HIV-1 protease substrates and non-substrates.</p><p>We discuss how proteochemometrics can be used to map recognition sites of entire protein families in great detail and demonstrate how it can incorporate target variability into drug discovery process. Finally, we assess the utility of the proteochemometric approach in evaluation of ADMET properties of drug candidates with a special focus on inhibition of cytochrome P450 enzymes and investigate application of the approach in the pharmacogenomics field.</p>
7

Modeling the Interaction Space of Biological Macromolecules: A Proteochemometric Approach : Applications for Drug Discovery and Development

Kontijevskis, Aleksejs January 2008 (has links)
Molecular interactions lie at the heart of myriad biological processes. Knowledge of molecular recognition processes and the ability to model and predict interactions of any biological molecule to any chemical compound are the key for better understanding of cell functions and discovery of more efficacious medicines. This thesis presents contributions to the development of a novel chemo-bioinformatics approach called proteochemometrics; a general method for interaction space analysis of biological macromolecules and their ligands. In this work we explore proteochemometrics-based interaction models over broad groups of protein families, evaluate their validity and scope, and compare proteochemometrics to traditional modeling approaches. Through the proteochemometric analysis of large interaction data sets of multiple retroviral proteases from various viral species we investigate complex mechanisms of drug resistance in HIV-1 and discover general physicochemical determinants of substrate cleavage efficiency and binding in retroviral proteases. We further demonstrate how global proteochemometric models can be used for design of protease inhibitors with broad activity on drug-resistant viral mutants, for monitoring drug resistance mechanisms in the physicochemical sense and prediction of potential HIV-1 evolution trajectories. We provide novel insights into the complexity of HIV-1 protease specificity by constructing a generalized IF-THEN rule model based on bioinformatics analysis of the largest set of HIV-1 protease substrates and non-substrates. We discuss how proteochemometrics can be used to map recognition sites of entire protein families in great detail and demonstrate how it can incorporate target variability into drug discovery process. Finally, we assess the utility of the proteochemometric approach in evaluation of ADMET properties of drug candidates with a special focus on inhibition of cytochrome P450 enzymes and investigate application of the approach in the pharmacogenomics field.

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