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You searched for subject:(Alpha conotoxin GID). One record found.

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RMIT University

1. Suresh, A. Computational design and studies of neuro-active peptides and the effects of calcium on nicotinic acetylcholine receptors in relation to neurodegenerative disorders.

Degree: 2016, RMIT University

Neuronal nicotinic acetylcholine receptors (nAChRs) are important ligand gated ion-channels in the brain that play important roles in inter-cellular communication and the release of neurotransmitters. However, these channels are also implicated in common neurodegenerative disorders such as Alzheimer’s and Parkinson’s diseases. The α7 and α4β2 subtypes of nAChRs are amongst the most prevalent subtypes in the brain. Given that Alzheimer’s disease (AD) is associated with a significant loss in α7 and α4 subunits, these subtypes are likely to play especially important roles in the pathophysiology of this disorder. A deeper understanding of the specific roles of these two receptors in AD would be possible with the availability of ligands which can modulate the activity of α7 and α4β2 in a subtype-specific manner. α-Conotoxins are a family of cysteine-rich peptides found in marine snails from the genus Conus. These small peptides act as antagonists to nAChRs, and some are able to discriminate between distinct nAChR subtypes. The α-conotoxin [γ4E]-GID is highly potent towards the human α7 nAChR, and is amongst the few known conotoxins which also inhibit α4β2. In this thesis, we use computer modelling and simulation techniques to 1) understand the interaction of α-conotoxin [γ4E]-GID with both α7 and α4β2 nAChRs at the canonical ligand binding site; 2) elucidate subtype-dependent conotoxin unbinding pathways, leading to identification of possible alternative sites which may serve as targets for rational conotoxin design; and 3) examine the influence of elevated calcium ion concentration on α7 structure and its interactions with [γ4E]-GID. Based on simulation data, we propose mutations to [γ4E]-GID which may lead to the design of a novel [γ4E]-GID-derived peptide with enhanced selective inhibition for α4β2. An introduction to neuronal nicotinic receptors and conotoxins along with a literature review of the important studies on receptor-conotoxin binding are presented in Chapter 1. The simulation methods, parameters used for this study and other derivative techniques, including umbrella sampling, that were employed in this study are described in Chapter 2. Current knowledge of the structure of the extracellular domain of the human α7 and human/rat α4β2 nicotinic receptors are presented in Chapter 3 along with protein interaction data derived from the simulation of the modelled toxin-bound receptor structures. From our simulations, several [γ4E]-GID residues were identified as being potentially amenable to improve selectivity of α4β2 over α7 by mutation. Results from recent experimental evidence are discussed, in which some of the [γ4E]-GID sites and mutants identified from…

Subjects/Keywords: Fields of Research; Alzheimer'; s disease; Alpha conotoxin GID; Molecular Dynamics Simulation; Nicotinic Acetylcholine Receptor; Calcium; Neuro-degenerative disorde; Computational Biology; Bioinformatics

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APA (6th Edition):

Suresh, A. (2016). Computational design and studies of neuro-active peptides and the effects of calcium on nicotinic acetylcholine receptors in relation to neurodegenerative disorders. (Thesis). RMIT University. Retrieved from http://researchbank.rmit.edu.au/view/rmit:162149

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16th Edition):

Suresh, A. “Computational design and studies of neuro-active peptides and the effects of calcium on nicotinic acetylcholine receptors in relation to neurodegenerative disorders.” 2016. Thesis, RMIT University. Accessed September 17, 2019. http://researchbank.rmit.edu.au/view/rmit:162149.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7th Edition):

Suresh, A. “Computational design and studies of neuro-active peptides and the effects of calcium on nicotinic acetylcholine receptors in relation to neurodegenerative disorders.” 2016. Web. 17 Sep 2019.

Vancouver:

Suresh A. Computational design and studies of neuro-active peptides and the effects of calcium on nicotinic acetylcholine receptors in relation to neurodegenerative disorders. [Internet] [Thesis]. RMIT University; 2016. [cited 2019 Sep 17]. Available from: http://researchbank.rmit.edu.au/view/rmit:162149.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Suresh A. Computational design and studies of neuro-active peptides and the effects of calcium on nicotinic acetylcholine receptors in relation to neurodegenerative disorders. [Thesis]. RMIT University; 2016. Available from: http://researchbank.rmit.edu.au/view/rmit:162149

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

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