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 37 for “"Structure-Based Drug Design"”.
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Structure-Based Drug Design Against a Biosecurity Pathogen
… inhibitor, including the first substrate bound structure. X-ray crystallography-based fragment screening is then applied, identifying a large number of binding fragments, bound not only to the active site but also an allosteric site. We show that binders inhibit enzyme activity, with promise for …
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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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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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Applications of Solid State Nuclear Magnetic Resonance Spectroscopy as a Tool for Structure Based Drug Design
The goal of this research is to establish new drug targets and inhibitors against pathogens responsible for tropical and infectious diseases. Farnesyl diphosphate synthase, which forms farnesyl diphosphate in the isoprenoid biosynthesis pathway, is an exciting new drug target because of its central …
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The Automatic Detection of Small Molecule Binding Hotspots on Proteins: Applying Hotspots to Structure-Based Drug Design
… site is an important first step in structure-guided drug discovery, but current methods typically assess the pocket as a whole, doing little to suggest which regions and interactions are the most important for binding. This thesis introduces Fragment Hotspot Maps, a grid-based method …
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!Development of small molecule therapeutics against anti-infectious and anti-cancer drug resistance via structure-based drug design
<p>!Drug discovery typically involves structure-based drug design based on three-dimensional protein structures and hit/lead compound identification and optimization. Herein, this technique was used to overcome several obstacles associated with the developing of antibiotics, anticancer agents, and …
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Structure-Based Drug Design in Medicinal Chemistry I. Development of Translesion Synthesis Inhibitors II. Synthesis and Biological Evaluation of Sulfonyl Piperazine Derivatives for LpxH Inhibition
… lead compound is a crucial step for the drug development. Despite of a number of approaches, the optimization of promising hit compounds is still challenging. Structure-based drug design approach is a well established and widely used strategy based on the 3D atomic structure of proteins. …
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Crystallographic, Molecular Dynamics, And Enzymatic Studies Of Multi-Drug Resistant Hiv-1 Protease And Implications For Structure Based Drug Design (project 1); Crystallographic Studies Of Human Myelin Protein Zero (project 2)
<p>Under drug selection pressure, emerging mutations render HIV-1 protease drug resistance, leading to the therapy failure in anti-HIV treatment.Tthe multidrug-resistant 769 (MDR) HIV-1 protease (resistant mutations at residues 10, 36, 46, 54, 62, 63, 71, 82, 84, 90) is selected for the present …
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Structure based design of a ricin antidote
… characterized, and is an attractive target for structure-based drug design. Aided by computer docking simulations, several ricin toxin A chain (RTA) inhibitors have been identified; the most promising leads belonging to the pterin family. To date, the most potent RTA inhibitors developed using …
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Molecular modelling assisted design and synthesis of cyclothialidine derivatives as DNA gyrase inhibitors
… new analogues have failed to prove that. In the structure based drug design stage, we designed a group of open chain cyclothialidine derivatives by applying the SPROUT programme and completed the syntheses. Improved activity is found in a few analogues and a 3D pharmacophore of the DNA gyrase B …
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Improving Protein Docking Using Efficient Sustainable Evolutionary Algorithm
… widely used automated protein docking program in structure-based drug-design. Different search algorithms, such as Simulated Annealing, traditional Genetic Algorithm and Lamarckian Genetic Algorithm are used in AutoDock. However, the docking performance of these algorithms is still limited by the …
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Efficient Biomolecular Computations Towards Applications in Drug Discovery
… research from many respects, including structure-based drug design. The ability of these methods to address biologically relevant problems is largely determined by the accuracy of the treatment of complex solvation effects in target biomolecules surrounded by water. The implicit solvent …
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Biochemical and computational studies towards selective inhibition of the immunoproteasome
… CP and IP specificity pockets (S1-4) allows structure-based drug design. The cyclic peptides argyrin A and F exhibit potent, reversible CP inhibition with mechanisms distinct to existing therapeutics. In this project, argyrin B inhibition and binding interactions between the CP and IP are …
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Design and Synthesis of Novel Small Molecule Drugs for the Treatment of Cancer and Osteoporosis
… of hepatocellular carcinoma. To construct the drug, we utilized a technique called small molecule drug conjugate, which combines the potency of the payload and the selectivity of the targeting moiety. We designed the conjugate using a potent tubulin inhibitor, veru-111, a targeting moiety …
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Approaches to lead generation for idiopathic pulmonary fibrosis targets
… as a treatment for IPF. Accordingly, a rational drug design approach was pursued with the aim of creating novel, simple molecules derived from these two progenitor compounds, whilst strategically retaining key pharmacophoric elements of AM095 and PF-8380 hypothesised to be crucial for activity. …
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Substrate binding to MshB, a zinc-dependent deacetylase in the mycothiol biosynthetic pathway of Mycobacterium tuberculosis
New drugs are needed to combat the ever-increasing incidence of drug resistant tuberculosis. Eukaryotes and Gram negative bacteria make use of a low molecular weight thiol-containing peptide, glutathione (GSH), in their defense against toxins and oxidative stress. In mycobacteria a …
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Improving of the accuracy and efficiency of implicit solvent models in Biomolecular Modeling
… practical applications such as biotechnology and structure-based drug design. One of the essential requirements of Biomolecular modeling is an accurate description of the solvent (water). The challenge is to make this description computationally facile that is reasonably fast, simple, robust and …
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Leveraging Local Perturbations to Map Allosteric Networks of Phosphatases
… small-molecule fragments binding to PTP1B. These structures also indicated that temperature can modulate protein conformational responses to ligand binding, leading to new insights into allosteric networks. Building on fragment-bound structures, I worked to apply structure based drug design (SBDD) …
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Computational Modeling of Rna-Small Molecule and Rna-Protein Interactions
… is restricted by lack of computational tools for structure-based drug design. To test the potential of translating molecular docking tools designed for protein to RNA-ligand docking and virtual screening, we benchmarked 5 docking software and 11 scoring functions to assess their performances in …
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