Molecular Simulations To Investigate Protective Mutations Of APOE Proteins

Principal Investigator: Qing Shao, contact information: [email protected], 159 F Paul Anderson Tower Department of Chemical and Materials Engineering, University of Kentucky, Lexington KY, 40506 Lead Institution: University of Kentucky Current academic rank/position: Assistant Professor Molecular simulations to investigate protective mutations of APOE proteins This project aims to probe how protective mutations of Apolipoprotein E (ApoE) affect protein conformation, protein-lipid interactions, and protein-receptor binding. ApoE proteins are composed of 299 amino acids and three ApoE proteins, ApoE2, 3, and 4, play an essential role in Alzheimer''s disease. Researchers have identified that several single-point mutations on these proteins can reduce the risks of Alzheimer''s disease but the related mechanisms remain unclear. Understanding these protective mutations could lay a foundation to design efficient treatments mimicking them. We hypothesize that these single-point mutations induce a variation in the conformation of the ApoE proteins and change the lipid binding and receptor recognition. We will test our hypothesis using computational approaches including alphaFold2, molecular dynamics simulations, and well-tempered metadynamics.