Cholesteryl ester transfer protein (CETP) mediates the transfer of cholesteryl esters (CE) and triglycerides (TG) between High Density Lipoproteins (HDL) and Low Density Lipoproteins (LDL). Recent studies have shown that blocking the function of CETP can increase the level of HDL in blood plasma and suppress the risk of cardiovascular disease (CVD).1 Hence, understanding the structure, dynamics, and mechanism by which CETP exchanges neutral lipids between HDL and LDL has received tremendous attention in last decade. In this work, we explored the large-scale dynamics of CETP by means of state-of-the-art molecular dynamics simulations. Results from atomistic simulations of CE-bound CETP complex show that CEs intra-convert between bent and linear conformations inside CETP core tunnel for quick and easy transfer.2 Results from inhibitor-bound CETP complexes suggest that physical occlusion of CETP's core tunnel by inhibitors is the primary mechanism of CETP inhibition.3 Coarse-grained simulations of HDL-CETP-LDL ternary complex is being performed for a more accurate understanding of the lipid transfer mechanisms of CE and TG between HDL and LDL through CETP. I will discuss some of these recent findings in my talk.

Lipid transfer mechanism of cholesteryl ester transfer protein between HDL and LDL

255th National Meeting (2018)

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