Virtual Screening Compounds to Discover EAAT2 Agonists for Trigeminal Neuralgia

Overview

Regarded as one of the most painful conditions for human beings, Trigeminal Neuralgia (TN) is a rare chronic pain disorder that affects the trigeminal nerve and induces excruciating facial pain. The rarity of the disease limits research incentive, and current ineffective drug treatments develop a necessity for further research in TN. Although the pathogenesis of TN is not completely understood, possible causes of TN are linked to high extracellular glutamate concentration. Research papers have shown that extracellular glutamate concentration is mainly maintained, or down-regulated, by excitatory amino acid transporters, specifically EAAT2, a subtype of EAAT. Chemicals bound to EAAT2 to enhance its activity would potentially provide more effective and safe treatments for TN. Chemical compound groups varying in molecular weight were tested for EAAT2 binding affinity: lower free energy values indicated stronger binding affinity. A virtual screening was conducted, utilizing open sources for building a homology model, downloading chemical compounds, and testing for binding affinity. There was a significant difference between the independent groups in free energy, thus supporting the hypothesis that chemical compound binding to EAAT2 could reduce glutamate concentrations, thus alleviating pain.