Department of Biochemistry, University of Oxford, United Kingdom.
Biophys J. 2010 Oct 20;99(8):2534-40. doi: 10.1016/j.bpj.2010.08.002.
Free energy profiles for insertion of a hydrophobic transmembrane protein α-helix (M2 from CFTR) into a lipid bilayer have been calculated using coarse-grained molecular dynamics simulations and umbrella sampling to yield potentials of mean force along a reaction path corresponding to translation of a helix across a lipid bilayer. The calculated free energy of insertion is smaller when a bilayer with a thinner hydrophobic region is used. The free energies of insertion from the potentials of mean force are compared with those derived from a number of hydrophobicity scales and with those derived from translocon-mediated insertion. This comparison supports recent models of translocon-mediated insertion and in particular suggests that: 1), helices in an about-to-be-inserted state may be located in a hydrophobic region somewhat thinner than the core of a lipid bilayer; and/or 2), helices in a not-to-be-inserted state may experience an environment more akin (e.g., in polarity/hydrophobicity) to the bilayer/water interface than to bulk water.
使用粗粒化分子动力学模拟和伞形采样计算了疏水性跨膜蛋白α-螺旋（CFTR 的 M2 ）插入脂质双层的自由能分布，以产生与穿过脂质双层的螺旋平移相对应的反应路径上的平均力势。当使用疏水区较薄的双层时，插入的自由能更小。从平均力势得出的插入自由能与许多疏水性标度得出的自由能以及跨膜转运蛋白介导的插入得出的自由能进行了比较。这种比较支持跨膜转运蛋白介导的插入的最新模型，特别是表明：1），即将插入的螺旋可能位于比脂质双层核心稍薄的疏水区；和/或 2），未插入的螺旋可能经历的环境与双层/水界面更相似（例如，极性/疏水性），而不是与纯水更相似。
