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.
Results
Showing 1 to 18 of 18 for “"Structure-based virtual screening"”.
-
Pharmacological Characterization of Novel Serotonin Transporter Inhibitors Identified Through Computational Structure-Based Virtual Screening
… work within this doctoral thesis encompasses a structure-based virtual screen targeting SERT and the pharmacological analysis of the compounds identified from the screen.</p> <p>Previous virtual screens utilized SERT homology models based on a bacterial leucine transporter as the structural …
-
STRUCTURE-BASED COMPUTATIONAL MODELING OF PROTEIN-LIGAND INTERACTIONS - APPLIED TO PROTEINS INVOLVED IN HUMAN DISEASES
Protein structure-based virtual screening of large chemical libraries is commonly performed against static X-ray and NMR structures. However, proteins are dynamic macromolecules occupying different conformational spaces. Consequently, different protein structures of the same protein could exhibit …
-
Computer-aided drug design and the biological evaluation of anti-cancer drugs
… 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 finding similar inhibitors to …
-
Rational Identification of Neuropilin-1 Inhibitors: From Deep-Learning to Drug Repurposing
… modelling, molecular dynamics simulations and structure-based virtual screening were integrated with biochemical and biophysical validations, followed by cell-based functional assays. In this way, the constraints of a shallow, highly polar and charged ligand-binding site could be engaged. The …
-
Improving ligand discovery using deep learning on three-dimensional structural data
… applications in drug discovery, emphasizing on structure-based 3D generative models that produce molecules based on binding pocket context for high-affinity molecule inception. In a first research chapter, I describe the application of atomistic neural network to rank conformations of molecules …
-
Trpv5: Structure, Function And Drug Discovery
… on TRPV5 which yielded the first reported structure of this protein. From that structure we were able to identify the econazole binding site and gain insights into how binding of a modulator in that pocket would result in channel inhibition. We then sought to elucidate the mechanism of …
-
Use of Structure-And Ligand-Based Drug Design Tools for the Discovery of Small Molecule Inhibitors of Cysteine Proteases for the Treatment of Malaria and Sars Infection
… , referred as Falcipains (FPs), by the structure-based virtual screening of the focused libraries enriched in soft-electrophiles containing compounds. Twenty one diverse, non-peptidic, low micromolar hits were identified. A combined data mining and combinatorial library synthesis …
-
Computational Methods to Identify and Target Druggable Binding Sites at Protein-Protein Interactions in the Human Proteome
… for the identification of hit compounds from structure-based virtual screening. The tight uPAR•uPA interaction offers a platform to test methods that leverage hot spots on both the protein receptor and ligand. A method is described that enriches for small molecules that both engage hot spots …
-
Computer-Aided Design of Ligands at Multiple Protein Targets for Multifactorial Diseases
… has remained elusive. To elucidate this, a structure-based virtual screening protocol was implemented to find chemically novel compounds with improved selectivity and a reduced side-effects profile. To develop methods for the discovery of multi-target ligands, a multi-target design approach, …
-
Computationally and Experimentally Exploring the Type IV Pilus Assembly ATPase for Antivirulence Drug Discovery
… of PilB. This work supports the use of PilB in structure-based virtual screening to identify novel compounds targeting PilB. Additionally, through heterologous expression and chromatography methods, the ATPase core of Neisseria gonorrhoeae PilF was successfully expressed and purified as an …
-
Molecular modeling and SAR studies of CDK5/p25 selective inhibitors
… we decided to achieve selectivity through structure based virtual screening strategy, validate the hits through biological screening and explore structure activity relationship (SAR) modifications around the lead structure. </p> <p>To identify de-novo templates, we decided to use the …
-
Discovery of Alternative Artemisinin Binding Sites in Plasmodium falciparum ATPase-6
… of the protein, rendering it dysfunctional. Structure-based virtual screening was then used to screen a commercial database of compounds to find novel inhibitors of PfATP6. Biological testing will be done to determine if targeting these new sites can produce potent antimalarials with less …
-
Protein-ligand interaction studies and identification of new drug-like hits as cannabinoid receptor modulators
… of allosteric site(s) in the CB2 receptor and screening of new CB2 allosteric modulators (AMs).</p> <p>Chapter 1 describes background information on cannabinoids and the endocannabinoid system. Chapter 2 focuses on the structure-activity relationships of Cannabis-derived ligands with CB1 and …
-
Targeting protein kinases to manage or prevent Alzheimer’s disease
… to construct 3D models for kinases whose crystal structures have not yet been identified. The information from structurally similar proteins was used to define the amino acid residues in the ATP binding site as well as other important sites and motifs. We searched for the comstructural motifs and …
-
Computational modeling-based discovery of novel classes of anti-inflammatory drugs that target lanthionine synthetase C-like protein 2
… and infectious diseases. A case for LANCL2-based drug discovery and development is also illustrated by the anti-inflammatory activity of novel LANCL2 ligands such as NSC61610 against inflammatory bowel disease in mice. This dissertation discusses the value of LANCL2 as a novel therapeutic …
-
Development of improved methodologies for the discovery of novel bioactive compounds and their application to problems of biomedical relevance.
… The principal objective on which this work is based is fundamentally to apply methodological improvements in chemoinformatic techniques for the discovery of new bioactive compounds against different therapeutic targets, both in an academic and industrial context. The computational techniques …
-
Structure-based development of novel chemical scaffolds as inhibitors of the store-operated calcium entry pathway
… SOCE inhibitors originate from phenotypic screening and derivatisation of some initial hits that were not much selective against the SOCE (Orai-mediated) and non-SOCE (TRPCs-mediated) pathway. Recently, few structures of the Drosophila Orai (DmOrai) have been published and I sought out to …
-
Stepwise Reconstitution of RNA Cellular Activity
… but there is debate as to whether the structures and activities of RNAs observed in vitro transfer to the cellular context. My thesis work seeks to probe these predictive relationships between in vitro and in vivo activity of viral RNAs and apply them to viral RNA-targeted drug …