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 20 of 187 for “"Binding pocket"”.
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Mutational studies in the dNTP binding pocket of human immunodeficiency virus type 1 reverse transcriptase
… The major defect seems to be at the substrate binding step as the processivity of these mutants was not affected while the extent of primer utilization correlated with the loss of their polymerase activity. Curiously, these mutant derivatives of Q91 were found to be highly resistant to ddNTPs …
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I. Design and synthesis of estrogen receptor gene switches. II. Design and synthesis of estrogen receptor ligands occupying an auxiliary binding pocket
… single mutations of ER residues near the ligand binding pocket were evaluated using modeling to predict the size and shape of the mutated binding pocket that would not bind estradiol. Ligands were designed, synthesized, and tested using a yeast two-hybrid assay to activate the mutated receptor to …
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Receptor- G Protein Interactions in the Visual System: A Study of Structures and Mechanisms That Couple the Cytoplasmic Surface of Rhodopsin to the Nucleotide-Binding Pocket of Transducin
… of the amino terminus of C4 were defective in binding holo-Gt, a peptide derived from the carboxyl terminus of Gαt, and in certain circumstances a peptide derived from the carboxyl terminus of Gγt. These results suggested that C4 mediated Gt binding and activation and that C4 interacted …
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Development and Application of Pseudoreceptor Modeling
… building a model representation of the protein pocket. However, the ability of pseudoreceptors to accurately replicate natural protein surfaces has not been studied. The goal of this thesis work is to investigate the necessary descriptors to map a protein binding pocket and a method to …
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Structure and dynamics of soluble guanylyl cyclase
… Prior experimental work has suggested two binding modes of YC- 1. In the current investigation, molecular dynamics simulations (MD) were conducted to seek more detail of molecular mechanism of sGC activation. From these MD simulations, a tentative mechanism of sGC activation is established. …
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Interactions and Functions of the Ubiquitin Specific Protease 7 in Human Cells
… to cancer. Our lab has previously discovered a binding pocket in the USP7 N-terminal TRAF domain that mediates interactions with target proteins. In this thesis I demonstrate how I contributed to the identification of a second binding pocket located in the Ubl2 ubiquitin-like structure of the …
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Computational rationale for the selective inhibition of the herpes simplex virus type 1 uracil-DNA glycosylase enzyme
In this thesis I will investigate the binding pocket and analyse the nature of binding of the 6-(4-Alkylanilino)-uracil inhibitors in hsvUDG and hUDG to provide a platform for the development of improved inhibitors.
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Understanding ligand binding, selectivity and functions on the G protein-coupled receptors: A molecular modeling approach
… and even receptor response upon ligand binding. The following dissertation examines the results from three different projects with varied objectives – i) structural modeling of human C-C chemokine receptor type 5 (CCR5) and assessment of the ligand binding pocket of the receptor, ii) …
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Investigation into the role of binding loop E on the function of the nematode cys-loop GABA receptor.
… thesis was to further characterize the agonist binding pocket in Hco-UNC-49BC, the LGCC gated by γ- aminobutyric acid (GABA) within H. contortus. To meet this objective, each amino acid residue in binding loop E was changed to a cysteine and analyzed via electrophysiology and the substituted …
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SK Channel Modulators as Drug Candidates and Pharmacological Tools
… weak in potency. Lack of knowledge about the binding site for the compounds is the main reason hindering the development of more potent and effective therapeutics targeting SK channels. Dr. Zhang and his colleagues recently discovered the binding pocket for these positive modulators of SK/IK …
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Characterization of Leucyl -Trna Synthetase From Homo Sapiens and Escherichia Coli in Aminoacylation, Amino Acid Editing and Interdomain Interactions
… analysis of the hscLeuRS focused on its editing pocket. The editing site of hscLeuRS includes a highly conserved threonine discriminator and universally conserved aspartic acid that were mutationally characterized. Substitution of threonine to alanine uncoupled specificity similar to other …
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Catalysis, substrate binding and specificity in the amidase from Nesterenkonia species
… on short aliphatic amide substrates by analyzing binding and interactions of these molecules with the NitN binding pocket. To probe the catalytic role of the two active site glutamate residues (Glu61 and Glu139) using NitN as a model enzyme. To monitor the activity, interactions and reactivity of …
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Stressed Out: Resistance-nodulation-division (RND) and Major Facilitator Superfamily (MFS) Efflux Pump Mediated Survival Strategies of Acinetobacter baumannii
… of AdeFGH and AdeJ of AdeIJK, and how specific binding pocket residues impact substrate specificity and export efficiency. I used biochemical methods such as cloning, mutagenesis, antibiotic susceptibility assays, inhibition studies, and fluorescence uptake assays to accomplish these goals. I …
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Regulation of Guanine Nucelotide Exchange in Inhibitory G Protein Alpha Subunit by Activator of G Protein Signaling 3 and Novel Regulatory Peptides
The release of GDP from the nucleotide binding pocket of G protein a subunit (Ga) is accelerated by guanine nucleotide exchange factors (GEFs) and inhibited by guanine nucleotide dissociation inhibitors (GDIs). The beta gamma subunit of heterotrimeric G protein and GoLoco motif are GDIs. Activator …
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Lariat peptide inhibitors of Abl kinase
… occupy the highly conserved adenine-binding pocket located in the kinase catalytic cleft, and therefore the target selectivity of these molecules is a major concern. In order to design highly specific next-generation drugs, it is essential to exploit the less-conserved binding …
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Improving ligand discovery using deep learning on three-dimensional structural data
… 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 tested in ligand-based or structure-based virtual screening, showing …
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Development of Combinatorial Approaches Towards Selective Estrogen Receptor Modulators: Investigations of Acyclic Amides and Tetra-Substituted Pyrazoles
… potentially favorable orientations in the ER binding pocket were synthesized. Among the four sites for basic side chain incorporation, the C (5) piperidinylethoxy-substituted pyrazole was found to have the highest affinity and to be an ERalpha antagonist, blocking the action of E2 with a …
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Rationalising the effect of guanine-based Ricin inhibitors using computer simulations
… inhibitors is the complete understanding of the binding pocket and the mode/nature of binding ligands to the protein. In this thesis computational methods were used to rationalise the effect of selected ricin inhibitors.
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Computational Study on MFP MexA in MexAB-OprM and RND transporter AcrB in AcrAB-TolC Efflux Pumps
… and the effects of mutations in the AcrB distal binding pocket. The starting point for the first part of our study was the uncertainty about the number of MexA proteins involved in MexAB-OprM assembly. Recent studies suggested the possibility for MexA to assemble into multimers, i.e. dimers, …
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Structure Activity Relationship Studies on Isoform Selective Sphingosine Kinase Inhibitors
… of blood S1P levels. The shape of the hSphK2 binding pocket was probed by introducing an indole moiety in place of the naphthyl ring and varying its substitution pattern. One key discovery from this study is SLC5101465 (hSphK2 Ki = 0.09 μM, > 111 fold SphK2 selective), which has a 1,5-indole …
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