胆固醇与环糊精包结的分子动力学模拟论文.pdfVIP

胆固醇与环糊精包结的分子动力学模拟 * 蔡文生 邵学广 （南开大学化学系，天津300071，中国） 摘要：本文用分子动力学(MD)模拟结合自适应偏置力(adaptive biasing force，ABF)方法考察了胆固醇与 β-CD, 2-羟丙基-β-CD(HP-β-CD)以及 2,6-二甲基 β-CD(DM-β-CD)包结过程中自由能沿某一指定反应路径的变化。在 主客体相互作用区间内积分平均力势 (potential of mean force，PMF)得到主客体包结的结合常数及相应的 结合自由能。研究结果表明，三种环糊精对胆固醇结合能力的次序为：DM-β-CD HP-β-CD β-CD。与实验 测定的结果一致。把 PMF 分解为各自由能组分能够帮助我们理解胆固醇是如何被包结进入环糊精空腔的。另 外，用额外的 MD 模拟研究了自由能稳态点处的包结结构，通过对 MD 运动轨迹的全面分析考察了此处包结结 构的稳定性。 Molecular Dynamics Study of the Inclusion of Cholesterol into Cyclodextrins CAI Wensheng, SHAO Xueguang (Department of Chemistry, Nankai University, Tianjin, 300071, P.R. China) Abstract: Cyclodextrins (CDs) have been used as tools to manipulate the lipid composition of biological and model membranes. Among the three families of CDs, β-CDs are known to be very efficient sterol-acceptor molecules, apparently because their inner hydrophobic cavity matches the size of the sterol molecule. β-CD derivatives have been shown to improve greatly solvation of sterols in aqueous solutions. The interaction of CDs with cholesterol has been investigated in detail, both at the theoretical and the experimental levels. Yet, despite the demonstrated effectiveness of CDs in biomedical applications, relatively little is known about the free energy change along the reaction pathway for cholesterol inclusion into CDs, or the detailed mechanism governing the latter. In this paper, the interaction of CDs with cholesterol is examined in aqueous solution. It is crucial to understand first the basic underlying mechanisms that drive cholesterol recognition and association with CDs. In this study, the interaction of β-CD, hept