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 17 of 17 for “"Druggability"”.
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Structures, Functions, and Druggability of the SARS-CoV-2 Replication–Transcription Complex
<p>Since its emergence in late 2019, the COVID-19 pandemic continues to devastate communities worldwide. Despite the successes in both identifying new therapeutics and immunization strategies that have alleviated the toll on livelihoods, the threat of novel coronavirus (CoV) variants triggering …
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Probing the druggability of the Notch1 ankyrin domain using a fragment-based approach
Notch signalling is a highly conserved pathway that is important in the developmental processes that control cell differentiation and cell fates. This canonical pathway involves binding of a transmembrane ligand in one cell to the extraceullular domain of a transmembrane Notch receptor in an …
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Small-molecule approaches to interrogate the druggability of the VHL E3 Cullin RING Ubiquitin Ligase
Protein-protein interactions (PPIs) are prevalent in Nature and so are attractive targets for chemical biology and drug discovery. Modulating PPIs is challenging because of the nature of their interacting surfaces. Nevertheless, recent progress has led to the discovery of small molecule modulators …
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Evolution of targets at the host-pathogen interface
… pan-genome genes with existing essentiality and druggability data, however, indicate that only a few proteins – 9 in this study – may be agreed upon as high confidence drug targets. Two protein targets were preliminarily assessed for their druggability: Mtb RecA protein (which contributes to …
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Structural Characterization of the Switch domain regions of Schistosoma mansoni druggable Adenylate cyclase-stimulating Gα-protein
… was to explore the solubility, stability and druggability of the Gα protein from the switch domain regions of S. mansoni. In-silico analysis of the switch domain regions using various bioinformatics tools has revealed the existence of two promising functional motifs which are highly conserved …
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Analysis of molecular interactions in the presence of side chain flexibility
… side chain analysis was used for predicting the druggability of protein-protein interaction targets and developing initial fragment hits into lead-like ligand molecules.
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Towards systems pharmacology models of druggable targets and disease mechanisms
… effective decisions on drug viability and target druggability and therefore attempt to reduce this time-consuming and costly attrition. Using text mining and text classification I present a growing landscape of systems pharmacology models in literature growing from humble roots because of …
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Analysis of the biophysical and in silico exploration of the interaction between small ribonucleoprotein G and the RING finger domain of retinoblastoma binding protein 6 for the identification of protein anti-cancer compounds
… results from this study suggest the potential druggability of the SNRPG~RING Finger domain PPI. These findings will enhance our understanding in selective identification of small molecule inhibitors or peptides, which could be developed as novel therapeutic candidates in the diagnosis and …
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Understanding small molecule-protein interactions
… the importance of a reliable way to predict druggability computationally. The second part of this dissertation shifts focus to the development of electrostatic models of small molecules. It is widely believed that classical potentials can describe neither vibrational frequency shifts in …
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Computational and Pharmacological Approaches to Design Novel Allosteric Thymidylate Synthase Inhibitors
… allosteric inhibitors of higher potency and druggability.</p>
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DEVELOPING SMALL-MOLECULE PROBES AND INHIBITORS FOR ADP-RIBOSE-BINDING PROTEINS
… highly desired to elucidate their function and druggability. In Chapter 2, I developed a robust fluorescent polarization (FP) assay that works for a variety of human and viral macrodomains, using an ADPr-based tracer molecule. In Chapter 3, I further optimized the tracer by incorporating the …
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Investigation of Narrow Spectrum Targets in Antibacterial Drug Discovery
… studies have been conducted supporting the druggability of CdFabK and indicating the potential for selective inhibition of CdFabK.</p>
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Detection and analysis of binding sites and protein-ligand interactions
… yield important insight into the dynamics and druggability of such binding sites. Finally, high throughput affinity purified, mass spectrometry data is evaluated for identification of protein-metabolite interactions (PMIs) in Escherichia coli. A detailed search for known PMIs in both the …
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Multimethodological approaches to tackle glycogen: therapeutic and modelling opportunities in Lafora disease
… docking was performed resulting in suboptimal druggability. Consequently, this crystallographic system emerged as a reliable platform for large-scale screenings. Thus, covalent ligands and fragments have been tested to identify PTG-interacting compounds. Different ligands resulted in the …
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Characterisation of calcium/calmodulin-dependent protein kinase kinase 2 in prostate cancer
… of AMPK. Thus, to progress the understanding and druggability of CaMKK2 in PCa we investigated novel interactors and functions of the kinase and developed novel inhibitors to improve on STO-609.<br/><br/>We have identified and validated two novel interactors of CaMKK2; Gemin4 and ARCN1. Gemin4 is …
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Cryo-EM as a Tool to Study the Diverse Interactome of Ku 70/80 in NHEJ and Beyond
… develop a drug discovery pipeline to examine the druggability of protein-protein interactions (PPIs) in NHEJ, given their diversity and crucial role in pathway progression, as seen from our cryo-EM work. I focused on one interaction, that of Ku with XLF. Through in silico docking and subsequent …
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Small Molecule Binding to Disordered Proteins
The human proteome includes many proteins that are entirely disordered or contain long disordered regions. Although these proteins are linked with many diseases, there are currently no clinically-approved drugs that have been shown to target these proteins in their monomeric forms. In fact, …