Modeling Huntington's Disease Using Molecular Dynamics Simulations

Abstract

Huntington’s Disease is a fatal neurodegenerative disease caused by abnormal aggregation of the Huntingtin protein (htt) in neurons, primarily led by the N17 domain. Research shows that N17 preferentially binds to regions of curvature on a lipid bilayer, but its mechanism is unknown. Coarse-grained molecular dynamics simulations allow insight into these curvature-sensing mechanisms. It was found that modulating the electrostatics of the lipid bilayer affects the ability of N17 to sense curvature. Other preliminary results show that mutating phenylalanine residues on N17 causes changes in curvature sensing. Thoroughly understanding the mechanisms of N17 and its electrostatic properties will hopefully bring researchers closer to uncovering therapeutics for Huntington’s.