CAREER: Computationally Illuminating the Molecular Interplay between N-glycosylation and Ion Channel Gating

About This Grant

With the support of the Chemistry of Life Processes program in the Division of Chemistry, Professor Li from the University of Mississippi is investigating the critical role of glycosylation in regulating ion channel function. These ion channels serve as essential cellular gatekeepers that control numerous vital physiological processes, from heartbeat to nerve signals. Glycosylation is a process where sugar molecules attach to proteins. While scientists have established that these sugar modifications significantly influence channel function, the precise mechanisms remain poorly understood due to their complex and dynamic nature. Using advanced computational modeling techniques, Dr. Li's team aims to create detailed molecular maps that reveal how these sugar modifications interact with and regulate ion channels at the atomic level. The project will create a training program for Mississippi students, particularly in the growing field of computational chemical biology, helping to build the next generation of scientists. By combining cutting-edge computational research with educational outreach, this work not only advances our understanding of fundamental cellular processes but also strengthens America's scientific workforce. This research project seeks to understand the effects of N-glycosylation on ion-channels by investigating atomic-level glycan-protein interactions using advanced molecular dynamics simulation techniques. At the atomic level, this study will reveal the chemical basis and molecular recognition of N-glycans governing ion channel gating. It will elucidate how the inherent flexibility and heterogeneity of glycans structurally impact the function of multiple ligand-gated and voltage-gated ion channels. At the molecular and cellular level, this research will address an understudied yet critical aspect of ion channel structure-function relationships, that is how isoform-specific N-glycosylation regulates subunit composition and gating behaviors, resulting in differential electrical signaling in the brain, heart, and muscle. Understanding how glycosylation impacts ion channels paves the way towards further elucidating the molecular mechanisms underlying channel function. This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.