2024 Student Research Conference:
37th Annual Student Research Conference

Using KCNQ2 structure to understand molecular determinants contributing to Developmental and Epileptic Encephalopathy

Emma C. Thompson
Dr. Timothy Abreo (Baylor College of Medicine), Dr. Edward Cooper (Baylor College of Medicine), and Dr. Bill R. Miller, Faculty Mentors

KCNQ neuronal heterotetramer potassium channels are essential for sensation, learning, memory, and action. Patients with KCNQ2 de novo missense mutations have a disorder called KCNQ2 epilepsy characterized by seizures and profound developmental delay. We focused on one mutation in which a glycine is changed to a tryptophan in the “turret” near the selectivity filter of the channel (G256W). Using modeling software, we analyzed residue interactions and torsion angles to understand the turret’s key bonding and configuration. Further analysis via molecular dynamics was performed to characterize the precise structural effects. The results imply that glycine’s flexible nature allows the turret to make a tight bend and form an extended network of hydrogen bonds that stabilize the open state of the selectivity filter. Tryptophan’s bulky side chain is rigid and nonpolar, likely destabilizing the turret and pore. Ultimately, this project explores the structural properties of G256W to understand its pathogenic effects.

Keywords: Epilepsy, Ion Channel Dysfunction, Computational Chemistry, Biochemistry

Topic(s):Biochemistry and Molecular Biology

Presentation Type: Oral Presentation

Session: 107-4
Location: MG 1000
Time: 10:00

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