胆固醇酯转移蛋白CETP是人类"头号杀手"心脑血管动脉粥样硬化疾病药物设计中的靶蛋白，其脂转运机理是一个关乎人类健康并亟待解决的重大问题。本项目拟采用分子动力学模拟方法，研究CETP传输胆固醇酯的物理机理。识别并表征CETP输运胆固醇酯的最优化路径，确定输运路径中势阱的位置与深度以及势垒的位置与高度，定位影响胆固醇酯传输的关键氨基酸位点。分析胆固醇酯传输过程中CETP整体和局部结构变化规律，探讨影响其传输的物理因素。分析胆固醇酯传输中潜在的中间态及其稳定性，研究如何通过调节中间态改变CETP的脂传输活性。探讨利用小分子阻止胆固醇酯传输，降低CETP活性的手段。研究胆固醇酯分子在CETP内传输的动力学特性，确认其在生理条件下穿越传输通道的物理原因，探讨CETP介导胆固醇酯转运的机理及调控CETP脂转运活性的方法。本项目研究对揭示脂转移物理规律、研发高效抗动脉粥样硬化药物都具有重要的科学意义。

Cholesteryl ester transfer protein (CETP) is the target protein for drug design to provent cardiovascular and cerebrovascular atherosclerotic disease that is ranked as number one human killer. The mechanism of cholesteryl esters (CE) transfer is a major and urgent scientific issues on human health. We will investigate the physical mechanism of CETP-mediated　cholesteryl esters (CE) transfer by means of molecule dynamics in this project. The optimal path of CE transfer in CETP will be recognized and characterized in the research. The depth and position of potential wells, and the height and position of potential barrier of CE transfer path will be determined quantitatively. The crucial amino acid sites to affect the CE transfer will be located. Through analyzing the global and local variations of CETP structure, the physical cause of CE transfer will be investigated. Having studied the latent intermediate states and their stability, we will further research how to change the CETP activity of CE transfer by adjusting the states. The way to hinder the CE transfer and reduce the activity of CETP will be discussed. By examinating the dynamics property of CE transfer, the physical cause of CE transfer will be investigated under physiological condition to reveal the mechanism of CE transfer mediated by CETP and the fashion of modulating the CETP activity. The studies in the project are scientifically significant on discovering the principle of CE transfer and developing drugs for anti-cardiovascular and cerebrovascular atherosclerotic disease.