The TRPC5 Golden Site: How Small Changes to a Ligand Affect Our Perceptions of Pain

Presenter

Aron Reuben Korsunsky

Campus

UMass Amherst

Sponsor

Jianhan Chen, Department of Chemistry, UMass Amherst

Schedule

Session 4, 2:30 PM - 3:15 PM [Schedule by Time][Poster Grid for Time/Location]

Location

Poster Board C14, Poster Showcase Room (163), Row 2 (C11-C20) [Poster Location Map]

Abstract

In our bodies, ion channels are crucial cellular components that regulate the flow of necessary ions in and out of the cell. Embedded in the cell's exterior membrane, ion channels permit the internal and external flow of potassium, calcium, chloride, etc. under one of several external factors. One family of ion channels, the transient receptor potential (TRP) channels, are defined by their multimodality; small molecules, extreme temperature, protons, and pressure are all common regulators of TRP channels. When a cell requires more calcium, for example, a cellular response may promote the opening of an ion channel, allowing calcium to flow into a cell or prevent it from exiting.

In diseased states, faulty ion channels cause uncontrollable ion flow. In these cases, external chemical ligands can force the channel into a closed or open state. One member of the TRP family, TRPC5, is poorly understood despite its relevance to tooth-related pain and its high prevalence in neurons. To better understand TRPC5 dynamics, this project studies TRPC5 in the presence of two known chemical ligands: riluzole, a TRPC5 activator currently used by ALS patients, and clemizole, a TRPC5 inhibitor currently in clinical trials for Dravet Syndrome. The mechanism of how these ligands influence TRPC5 is unclear; using molecular dynamics (MD), this project simulates the behavior of TRPC5 with riluzole and clemizole and aims to discover the relevant mode of action.

Keywords

Biophysics, Molecular dynamics, Ion channels, Disease

Research Area

Genetics

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