Using Chemical Library Screening and a Validated Docking Procedure to Identify Novel Aminoimidazole-based Human Arginase I Inhibitors
Date of Award
Master of Science (MS)
Joseph Audie, Ph.D.
The purpose of this study is to use virtual screening strategies to predict novel arginase inhibitors. This was accomplished by applying a validated protein-ligand docking procedure, chemical library filtering and computational ADMET calculations. Arginase enzymatically converts L-arginine into ornithine and urea and has been linked to numerous diseases. Due to the fact that arginase I is linked to various diseases, it is vital for inhibitors to be discovered. The docking procedure was validated by reproducing the inhibition results derived from the dietary flavonoid arginase inhibitors fisetin, luteolin and their derived compounds. Aminoimidazole amino acid inhibitors of arginase were analyzed in a similar fashion. Finally, Vina docking was validates in a re-docking study that involved reproducing x-ray poses for four arginase-ligand complexes. The validated Vina docking procedure was used to dock candidate amino-imidazole similar compounds culled from the ChemSpider chemical database. This resulted in the identification of 33 compounds that were further analyzed for their predicted toxicities and oral bioavailability properties using the admetSAR server. Ultimately, a single amino-imidazole mimetic (AIM3) was identified. Further research will focus on testing AIM3.
Tescione, Angelica, "Using Chemical Library Screening and a Validated Docking Procedure to Identify Novel Aminoimidazole-based Human Arginase I Inhibitors" (2016). Chemistry Master’s Theses. 51.