38th Annual Student Research Conference
Investigation of the Pathogenic Consequences for the KCNQ2 Developmental and Epileptic Encephalopathy Variant G256W in silico
Emma C. Thompson
Dr. Brian Lamp, Faculty Mentor
KCNQ potassium channels in the brain are essential for regulating electrical signals for sensation, learning, memory, and action. de novo KCNQ2 variants cause disruptions in neuronal ion channels formed by coassembly of homotetrameric KCNQ2 subunits or by a heterotetrameric combination with KCNQ3 subunits. Patients with KCNQ2 variants may be affected with KCNQ2 developmental and epileptic encephalopathy (KCNQ2 DEE) characterized by seizures and developmental delay. This study focuses on a particular variant located in the turret region of the pore domain called G256W. Molecular dynamics simulations were conducted to investigate the structural and functional effects of the tryptophan substitution. Various analyses such as hydrogen bond and pairwise energy interactions, Hole pore diagram visualizations, solvent accessible surface area calculations, and per residue fluctuations were performed and compared between wild type and variant simulations. Ultimately, this project explores the structural properties of G256W to understand its pathogenic effects.
Keywords: Computational Chemistry, Channelopathy Research, KCNQ2 Epilepsy, Molecular Dynamics
Topic(s):Biochemistry and Molecular Biology
Presentation Type: Oral Presentation
Session: 308-4
Location: MG 1000
Time: 1:45