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Defense Date
2003
DOI
https://doi.org/10.25772/5W13-JF38
Document Type
Dissertation
Degree Name
Doctor of Philosophy
Department
Chemistry
First Advisor
Dr. Donald D. Shillady
Second Advisor
Dr. Sarah C. Rutan
Abstract
The binding energies and Gibbs free energies ofbinding for melatonin and other indole-,naphthalene-, and benzene-moiety ligands totrans-membrane sections of the seven-helix humanmelatonin receptor MT1 have been calculated atthe ab initio and semi-empirical levels using GAMESS, and with molecular mechanics using Sybyl. A linear relationship was found between the Sybyl-calculated binding energies and theexperimentally-determined pKi values, and alinear fit of calculated HINT scores to theexperimentally-measured ΔG values givesdeltaG = -0.00263Hscore - 9.477, in kcal/mol. In addition, the interactions between individual residues in MT1 and various ligands were examined to determine why some ligands bind more strongly to MT1 than others. The magnetic circular dichroism spectra of melatonin bound tofragments of MT1 were also calculated, in theCNDO/S-D approximation.
Rights
© The Author
Is Part Of
VCU University Archives
Is Part Of
VCU Theses and Dissertations
Date of Submission
June 2008
VCU Only:
Off Campus Download
Comments
Part of Retrospective ETD Collection, restricted to VCU only.