Ms. Missy Mathis (Aergis Science Corporation)
Aegis Sciences Corporation is a forensic toxicology and healthcare company that was founded in 1990 and located in Nashville, TN. Aegis provides science-driven drug testing and consulting services. The healthcare laboratory is dedicated to making a difference in people’s lives by offering drug testing that provides information about patients’ medication adherence, which aides healthcare providers in the treatment and care of their patients. In addition to medication compliance, Aegis offers sports testing, substance abuse detection, and drug-drug interaction testing in urine, oral fluid, or blood specimens. Currently, Aegis has nearly 1,000 team members dedicated to serving our clients, which includes healthcare providers, professional and amateur sports organizations, university athletic departments, and others.
Ms. Paige Castleman (The University of Memphis)
Collaborative Computational Efforts: Benchmarking for Orphan G Protein Coupled Receptor Ligand Discovery
Abstract: G-Protein Coupled Receptors (GPCR) comprise a superfamily of over 800 integral membrane proteins with roles in cellular biochemistry and pathophysiology. With approximately 35% of FDA approved pharmaceuticals targeting GPCR and ~10% of GPCR being orphans that lack known endogenous activators, ligand identification for orphan GPCR is of utmost importance to enable additional work that will elucidate the role of orphan GPCR in normal human physiology and disease. Two computational methods used in ligand identification studies, homology modeling and pharmacophore modeling, have been benchmarked during lab standard operating procedure development. GPCR ligand interaction studies often have a starting point with either crystal structures or homology models. The majority of GPCR do not have experimentally-characterized 3-dimensional structures, so homology modeling is a good structure-based starting point. Homology modeling is a widely used method for generating models of proteins with unknown structures by analogy to crystallized proteins that are expected to exhibit structural conservation. Traditionally, homology modeling template selection is based on global sequence identity and shared function. However, after further examination, high sequence identity localized to the ligand binding pocket was shown to produce better models for examination of protein-ligand interactions. Additionally, ligand-based pharmacophore modeling, an in silico method that uses comparisons of known ligand structures to generate models relating positions of common functional groups in three dimensions, in combination with database mining is frequently used to identify candidate ligands for subsequent in vitro and in vivo validation. Another benchmark study examined the potential to develop functionally-biased pharmacophores using ligands of same (or mixed) function with current datasets and methods, and established a pharmacophore development protocol for the identification of novel GPCR ligands. The results of these computational benchmark studies have been/will be used to guide the ligand identification efforts of multiple orphan GPCR within our lab group.