Date of Award

2012

Document Type

Thesis

Degree Name

Master of Science (MS)

Department

Computer Science

First Advisor

Smith, Mary Dr.

Abstract

Peroxisome Proliferator-activated Receptors (PPARs) are ligand-activated nuclear receptors known for their major role in metabolic syndrome (MS). Abdominal obesity, high blood pressure, increased glucose levels and low concentrations of high-density lipoprotein characterize MS. Numerous studies proposed developing pan-agonists as potent drug candidates for the treatment and control of metabolic syndrome. The objective of this study was to use virtual screening with molecular docking to identify potential pan-PPAR ligands from the ZINC database. The 3D structural files of the receptor ligand binding domains (LBD), obtained from the Protein Data Bank (PDB), were energetically minimized and the binding pockets on each LBD were identified and measured. The screening was performed by docking each compound from the lead-like database to the LBD of the three receptors using the AutoDock software. The evaluation of the docking was based on the free energy of binding, position of the compound inside the binding pocket, and the protein residues that were involved in the binding. Twenty-seven out of approximately four million lead-like compounds were found to position themselves very well in the binding pockets of the three PPARs with minimal free energy of binding. These pan-PPAR ligands may be strong candidates as pan-PPAR agonists that should be investigated further.

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