Robinson A J, Richards W G, Thomas P J, Hann M M
Physical Chemistry Laboratory, Oxford University, United Kingdom.
Biophys J. 1995 Jan;68(1):164-70. doi: 10.1016/S0006-3495(95)80171-2.
Cholesterol molecules were put into a computer-modeled hydrated bilayer of dimyristoyl phosphatidyl choline molecules, and molecular dynamics simulations were run to characterize the effect of this important molecule on membrane structure and dynamics. The effect was judged by observing differences in order parameters, tilt angles, and the fraction of gauche bonds along the hydrocarbon chains between lipids adjacent to cholesterol molecules and comparing them with those further away. It was observed that cholesterol causes an increase in the fraction of trans dihedrals and motional ordering of chains close to the rigid steroid ring system with a decrease in the kink population. The hydrogen-bonding interactions between cholesterol and lipid molecules were determined from radial distribution calculations and showed the cholesterol hydroxyl groups either solvated by water, or forming hydrogen bond contacts with the oxygens of lipid carbonyl and phosphate groups. The dynamics and conformation of the cholesterol molecules were investigated and it was seen that they had a smaller tilt with respect to the bilayer normal than the lipid chains and furthermore that the hydrocarbon tail of the cholesterol was conformationally flexible.
将胆固醇分子置于由二肉豆蔻酰磷脂酰胆碱分子构成的计算机模拟水合双分子层中，并进行分子动力学模拟，以表征这种重要分子对膜结构和动力学的影响。通过观察与胆固醇分子相邻的脂质之间沿烃链的序参数、倾斜角和gauche键分数的差异，并将其与距离较远的脂质进行比较来判断这种影响。观察到胆固醇会导致反式二面角分数增加，靠近刚性甾体环系统的链的运动有序性增加，扭结数量减少。通过径向分布计算确定了胆固醇与脂质分子之间的氢键相互作用，结果表明胆固醇羟基要么被水溶剂化，要么与脂质羰基和磷酸基团的氧形成氢键接触。对胆固醇分子的动力学和构象进行了研究，发现它们相对于双分子层法线的倾斜度比脂质链小，而且胆固醇的烃尾在构象上具有灵活性。
