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.
| Identifer | oai:union.ndltd.org:vcu.edu/oai:scholarscompass.vcu.edu:etd_retro-1133 |
| Date | 01 January 2003 |
| Creators | Castevens, Charles Montgomery, IV |
| Publisher | VCU Scholars Compass |
| Source Sets | Virginia Commonwealth University |
| Detected Language | English |
| Type | text |
| Format | application/pdf |
| Source | Retrospective ETD Collection |
| Rights | © The Author |
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