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Date of Award

Spring 2011

Document Type

Restricted Thesis: Campus only access

Degree Name

Bachelor of Science

Department

Biochemistry & Molecular Biol.

First Advisor

Dr. Carol Parish

Second Advisor

Dr. Lisa Gentile

Abstract

Ionotropic glutamate receptors, a family of ligand gated ion channels, are located in the post-synaptic neural membrane and play important roles in the majority of fast excitatory neurotransmissions in the central nervous system. This family is comprised of three different subfamilies that each serve distinct roles at glutamatergic synapses. AMPA receptors mediate fast depolarization, NMDA receptors mediate the slower component of the excitatory postsynaptic potential, and kainate receptors have a major fast modulatory role at both presynaptic and postsynaptic sites. Binding of the neurotransmitter glutamate to an extracellular binding site on these receptors causes a conformational change which opens a pore, thus allowing cations to flow into the post-synaptic neural cell. Since glutamate is the major excitatory neurotransmitter in the central nervous system, the level of activity of iGluRs is tightly controlled. Mis-regulation has been implicated in schizophrenia, and Alzheimer’s, Huntington’s, and Parkinson’s diseases. Computational tools can be utilized in cooperation with experimental techniques to understand the atomistic nature and structural behavior of glutamate receptors.

The research described here utilizes homology and RMSD comparison methods to develop, test, and refine a three dimensional model based on a known iGluR crystal structure. Energy minimization was used to prepare the generated model structures for testing using molecular dynamics in order to evaluate the structure and dynamics of NMDA receptors which have binding sites in their S1S2 ligand-binding core and amino-terminal domains. The information gained will be used to further the examination of the structure and function of glutamate receptors and the interaction with their ligands.

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