Global ETD Search
Search theses and dissertations gathered from participating repositories worldwide. Every result links back to the library that holds it. No account is needed.
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Showing 1 to 20 of 413 for “"Drug design"”.
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Computer-Aided Drug Design of G-quadruplex Structures: Harnessing Polarization for Rational Drug Design
… dissertation focuses on improving the rational design of GQ-binding ligands by advancing computational methods that better capture the structural and electrostatic properties of GQs. Central to this effort is the use of the classical Drude oscillator polarizable force field model to more …
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Structure-Based Drug Design Against a Biosecurity Pathogen
Coxiella burnetii, a gram-negative Gammaproteobacterium, causes the human disease Q-fever. It displays a biphasic lifestyle, with a metabolically constrained small cell variant form enabling survival in the environment. Infection through aerosolization triggers conversion to the metabolically …
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Structure Based Drug Design of High Affinity Kras Inhibitors
… RAS has been aggressively targeted with drug design efforts for more than 30 years an FDA approved direct inhibitor has not yet been developed. There are three isoforms of RAS in cells; HRAS, NRAS and KRAS. We focused on KRAS since it is the most frequently mutated isoform in cancer. To …
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Computer-aided chemical speciation in metal-based drug design
Formation constants of Cu²⁺, Ni²⁺, Zn²⁺, Ca²⁺ and Gd³⁺ with the polyamine(amide) ligands N,N' -bis(2-hydroxyiminopropionyl) propane-1,3-diamine (L² ) and (1, 15)- bis(N,N-dimethyl)-5, 11-dioxo-8-(N-benzyl)-l ,4,8, 12, 15-pentaazapentadecane (L³ ) as well as those of Gd³⁺ with …
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Strategies for targeting cancer: small molecules, epigenetics and drug design
… These chemical cocktail treatments, designed to kill cancer cells, started in the late-1900s and even today remain a major line of defense in fighting this disease. The goal of the research described in this dissertation was to investigate current methodologies and techniques used to …
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Computational approaches for drug design at the Protein-Protein interface
The ability to design drugs that disrupt formation of protein-protein interfaces is of particular interest to the pharmaceutical industry due to its promise for opening an entire new range of drug targets, many of which have already been well characterised in terms of their disease causing effect …
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Accelerated simulations and computer-aided drug design of membrane proteins
… ~30% of the proteome and more than 60% of drug targets. They play key roles in physiological functions, such as signal transduction, transport, ion regulation and enzymatic activities. Malfunction of these proteins result in deadly human diseases, such as paralysis, cancer, heart failure …
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Dynamic Molecular Mechanisms and Drug Design of Important Therapeutic Targets
… GPCRs constitute the largest family of drug targets. The CXCR4 chemokine receptor, in particular, helps promote HIV entry into host cells. Polycystin-1 (PC1) is an atypical GPCR with 11 transmembrane domains. Mutations in the PC1 protein are responsible for the majority cases of a …
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Application of molecular mechanics polarization to fragment based drug design.
Polarization is a term that is often excluded from almost all virtual screening. Polarizability helps explain interactions between nonpolar atoms and electrically charged species. When studying fragments in FBDD these minor interactions could have large effect in changing how well a ligand will …
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Random forests and their application to heteroscedastic drug design data
… are widely used on tabular data, particularly drug design datasets. Whilst they often give good predictions they are difficult to interpret and the reasons for their successes and failures on different datasets are not always clear. This thesis explores this problem, providing an explanation …
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Improving de novo molecule generation for structure-based drug design
*De novo* molecule generation for drug design has seen a resurgence in recent years, mostly due to the rapid advances in machine learning (ML) algorithms that utilise deep neural networks, resulting in a plethora of ML-based generative models. However, there is often a large disparity in published …
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Identification and Inhibition of Fosfomycin Resistance Enzymes for Structure-Based Drug Design
… companies turning away from the traditional drug development pipeline. One alternative method to address AMR is through repurposing existing approved drugs such as by utilizing combination drug therapies. Combination drug therapies often involve the inhibition of antibiotic modifying enzymes …
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Great Expectations: Phosph(On)Ate Prodrugs In Drug Design—Opportunities and Limitations
… chemical moieties are being investigated in the design of novel inhibitors with antineoplastic potential. A central challenge to the delivery of phosph(on)ate-containing drugs is their anionic character at physiological pH, which portends poor membrane permeability. This limitation has been …
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Modeling protein flexibility using collective modes of motion: Applications to drug design
This work shows how to decrease the complexity of modeling flexibility in proteins by reducing the number of dimensions necessary to model important macromolecular motions such as the induced fit process. Induced fit occurs during the binding of a protein to other proteins, nucleic acids or small …
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Computer-aided drug design and the biological evaluation of anti-cancer drugs
Computer-aided drug design has become a promising alternative to high-throughput screening by identifying potential hits in silico for in vitro evaluation. In this study a combination of ligand-based and structure-based virtual screening was performed to identify in silico hits. This was based on …
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Application of continuous improvement methodologies and techniques in the Drug Design Cycle
… to better serve its patients by providing new drugs sooner, and to ensure its competitiveness for years to come. One way is to increase the efficiency within Research & Development (R&D), specifically within the Drug Design Cycle (DDC). This is driven by the fact that the average development …
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Study of the aryl hydrocarbon receptor as a target for rational drug design
<p>The aryl hydrocarbon receptor (AhR) heterodimerizes with the aryl hydrocarbon receptor nuclear translocator (Arnt) for transcriptional regulation. We generated three N-terminal deletion constructs of the human AhR of 12-24 KDa in size—namely D1 (aa 84-295), D2 (aa 84-192) and D3 (aa 191-295)—to …
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Mimicry of Cocaine by Anti -Idiotypic Antibodies: Molecular Basis and Antagonist Drug Design
[M. Ho was supported by National Research Service Award Predoctoral Fellowship F31-DA14484 from the National Institutes of Health, University of Illinois Fellowship (1-1-10742) and On-Campus Dissertation Research Grant (1-2-16449). This work was supported by NIDA research grant R15-DA10367 and …
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Refining computer-aided drug design routes for probing difficult protein targets and interfaces
… cancer treatments options are limited due to drug resistance, requiring additional drug development to improve patient survival rates. It is necessary to continuously develop new therapeutic approaches and identify novel targets, as cancer is ever-growing and adapting. Experimental research …
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Biochemical, Structural, And Drug Design Studies Of Multi-Drug Resistant Hiv-1 Therapeutic Targets
… the structural mechanisms that lead to multi-drug resistance to HIV-1 protease and integrase inhibitors. </p> <p>Proper proteolytic processing of the HIV-1 Gag/Pol polyprotein is required for HIV infection and viral replication. This feature has made HIV-1 protease an attractive target for …
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