Journal of Proteomics & Bioinformatics
Open Access

Molecular dynamics study on cholesteryl ester transfer protein

6^th International Conference on Structural Biology

August 22-23, 2016 New Orleans, USA

Shengli Zhang, Dongsheng Lei, Lei Zhang and Gang Ren

Xi�an Jiaotong University, China

Posters & Accepted Abstracts: J Proteomics Bioinform

Abstract :

Cholesteryl ester transfer protein (CETP) decreases the level of atheroprotective high-density lipoprotein cholesterol (HDL-C) while elevating the level of atherogenic low-density lipoprotein cholesterol (LDL-C). Several CETP inhibitors have been evaluated in large-scale clinical trials for treating cardiovascular diseases (CVDs) within the last decade. Although the structure of mutated CETP has been revealed through electron microscopy (EM) and the X-ray crystallography, the structure of native CETP in physiological conditions and the detailed mechanism of how CE transfers from HDL to LDL at atomic resolution remains unclear. Here, we employed all-atom molecular dynamics simulations to study the native CETP structure and CE transfer mechanism. We propose the structure of native CETP, which is more different in some aspects with the crystal structure. The simulation results showed that the tunnel is sufficiently large to mediate the transfer of a CE molecule through CETP with a predicted transfer rate comparable to physiological measurements. Analyses of the interactions and energies between the CE and CETP tunnel during transfer indicated several residues that might regulate CETP function during CE transfer. This study provides insight into the CE transfer mechanism for future development of CETP inhibitors.

Biography :

Email: zhangsl@mail.xjtu.edu.cn