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目的通过研究丹参酮IIA与胆固醇酯转运蛋白(CETP)的相互作用,探索其对CETP的影响模式。方法基于晶体结构构建丹参酮IIA与CETP多种形式的复合结构,并以此为起始结构进行分子动力学模拟,模拟软件为Gromacs 4.0,力场Gromos 96 53a6,温度300 K,模拟时间20 ns,记录轨迹,分析CETP整体形状和局部结构变化,考察丹参酮IIA与CETP的相互作用能量。结果磷酯酰胆碱出口区和空腔都装满后CETP结构比较刚性,单装空腔CETP结构容易变化。对应于CETP框架结构的形态变化,在与不同配体复合形式下CETP两侧的出口区和磷酯酰胆碱出口区以及空腔差异较大,丹参酮IIA与CETP相互作用较强的情况出现在2个磷酯酰胆碱出口位置和空腔左侧位置。结论 CETP是一个结构比较容易变化的载体蛋白,受装载配体结构和数量的影响容易发生相应变化,丹参酮IIA可能具有通过与磷酯酰胆碱或胆固醇酯共同作用影响CETP的形态,从而抑制其转运的能力。
OBJECTIVE: To investigate the effect of tanshinone IIA on CETP by investigating the interaction between tanshinone IIA and cholesterol ester transporter (CETP). Methods Based on the crystal structure, the complex structure of tanshinone IIA and CETP was constructed and used as the starting structure for molecular dynamics simulation. The simulation software was Gromacs 4.0, force field Gromos 96 53a6, temperature 300 K, simulation time 20 ns, Record the trajectory, analyze the overall shape and local structure changes of CETP and investigate the energy of interaction between tanshinone IIA and CETP. Results The structure of CETP was relatively rigid after the phosphatidylcholine outlet region and the cavity were full, and the CETP structure of the cavity was easily changed. Corresponding to the morphological changes of the CETP framework structure, the exit region and the phosphatidylcholine exit region and cavities on both sides of CETP with different ligand complex forms are quite different, and the interaction between Tanshinone IIA and CETP is strong 2 phosphatidylcholine outlet position and the left position of the cavity. Conclusion CETP is a relatively easy to change the structure of the carrier protein, the structure and quantity of the loading ligand prone to change accordingly, tanshinone IIA may have associated with phosphatidylcholine or cholesterol esters affect the morphology of CETP, thereby inhibiting its Transport ability.