(691b) Molecular Simulations of Activating and Inhibitory Protein Interactions in Triglyceride-Rich Lipoprotein Metabolism
AIChE Annual Meeting
2022
2022 Annual Meeting
Engineering Sciences and Fundamentals
Modeling of Lipid Membranes and Membrane Proteins
Friday, November 18, 2022 - 8:15am to 8:30am
Herein, we describe the use of molecular dynamics (MD) simulations to investigate the underlying mechanisms of LPL regulation, which remain largely unknown. Specifically, MD simulations were employed to investigate the molecular-level interactions between LPL, apoC-II, and ANGPTL4 and to determine how these interactions are modified in the presence of one another. Our simulations illustrate potential binding mechanisms between these three molecules, which can be confirmed with experiments using synthetic peptides that resemble the binding residues of ANGPTL4 and apoC-II. Qualitative trends are drawn between the activating and inhibitory mechanisms of the LPL-bound proteins, which can be applied to other regulators, like apoC-I or GP1HBP1, that work to stabilize or disrupt LPL in its metabolism of TRL. Ultimately, insights from these simulations may serve to guide the design of novel pharmaceuticals for treating or preventing HTG-related diseases.