Date of Award

9-15-2015

Document Type

Dissertation

Degree Name

Doctor of Philosophy (PhD)

Department

Bioinformatics

First Advisor

Jerry Darsey

Abstract

Traditional medicinal knowledge originated when ancient humans began treating their ailments and those of their livestock by systematically using plants and/or plant extracts. This knowledge has been transmitted across generations by verbal testimony and in writing through Vedic manuscripts. This study was undertaken to conserve the traditional medicinal knowledge and to evaluate the applications of traditional treatments on current systems of medical practice. Medicinal plant inventory was prepared with plants collected from five different states of southern India: Telangana, Andhrapradesh, Tamilnadu, Karnataka, and Kerala. The collected medicinal plants were classified and segregated based on the ailments these plants treat. Further, the molecular and metabolic mechanisms of the ailments were studied to identify a therapeutic protein target such as an enzyme, nuclear receptor, or an ion channel. I evaluated the known active chemicals in the plants and their extracts as basic fundamentals of pharmacokinetics, which then expanded by in silico molecular modeling studies and quantum mechanical calculations. The phytochemicals were screened and ranked using scores from molecular docking, this lead to the identification of potentially active compounds that warranted further inspection. Density Functional Theory (DFT) and Ab-initio calculations performed on the chemical constituents have provided important insight into excitation energy, total energy, dipole moment, and vibrational spectra of the molecules. DFT studies with geometry optimization revealed molecular geometry and steric repulsions within molecules. Ab-initio calculations predicted optimal geometries, theoretical infrared spectra, Raman intensities, and vibrational frequencies for each conformer. Genealogical trees were generated with Maximum likelihood, Neighbor-Joining (NJ), Minimum Evolution (ME), Unweighted Pair Group Method with Arithmetic Mean (UPGMA), Maximum Parsimony, and Bayesian methods. Results obtained for most varieties of plant genera demonstrated a significant positive correlation between phylogeny, chemical diversity, and medicinal activity or biological activity. Data collected from various studies (ethnobotanical, taxonomical, molecular modeling, quantum mechanical, phylogenetic) are organized into a Comprehensive Archive of Medicinal Plants (CAMP). CAMP utilizes multiple platforms for interactive 3D visualization of chemicals, their structures in the binding pocket of the corresponding cognate cellular targets, and the dynamic simulations of the most active chemical constituent for each medicinal plant.

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