Woolf T B, Roux B
Membrane Transport Research Group (GRTM), Department of Physics, Université de Montréal, Canada.
Proteins. 1996 Jan;24(1):92-114. doi: 10.1002/(SICI)1097-0134(199601)24:1<92::AID-PROT7>3.0.CO;2-Q.
The microscopic details of lipid-protein interactions are examined using molecular dynamics simulations of the gramicidin A channel embedded in a fully hydrated dimyristoyl phosphatidylcholine (DMPC) bilayer. A novel construction protocol was used to assemble the initial configurations of the membrane protein complex for the simulations. Three hundred systems were constructed with different initial lipid placement and conformations. Seven systems were simulated with molecular dynamics. One system was simulated for a total of 600 psec, four were simulated for 300 psec, and two for 100 psec. Analysis of the resulting trajectories shows that the bulk solvent-membrane interface region is much broader than traditionally pictured in simplified continuum theories: its width is almost 15 angstroms. In addition, lipid-protein interactions are far more varied, both structurally and energetically, than is usually assumed: the total interaction energy between the gramicidin A and the individual lipids varies from 0 to -50 kcal/mol. The deuterium quadrupolar splittings of the lipid acyl chains calculated from the trajectories are in good agreement with experimental data. The lipid chains in direct contact with the GA are ordered but the effect is not uniform due to the irregular surface of the protein. Energy decompositions shows that the most energetically favorable interactions between lipid and protein involve nearly equal contributions from van der Waals and electrostatic interactions. The tryptophans, located near the bulk-membrane interface, appear to be particularly important in mediating both hydrogen bonding interactions with the lipid glycerol backbone and water and also in forming favorable van der Waals contacts with the hydrocarbon chains. In contrast, the interactions of the leucine residues with the lipids, also located near the interface, are dominated by van der Waals interactions with the hydrocarbon lipid chains.
利用嵌入完全水合的二肉豆蔻酰磷脂酰胆碱（DMPC）双层中的短杆菌肽A通道的分子动力学模拟，研究了脂质-蛋白质相互作用的微观细节。一种新颖的构建方案用于组装用于模拟的膜蛋白复合物的初始构型。构建了300个具有不同初始脂质位置和构象的系统。用分子动力学模拟了7个系统。一个系统总共模拟了600皮秒，四个系统模拟了300皮秒，两个系统模拟了100皮秒。对所得轨迹的分析表明，本体溶剂-膜界面区域比简化连续介质理论中传统描绘的要宽得多：其宽度几乎为15埃。此外，脂质-蛋白质相互作用在结构和能量方面的变化远比通常假设的要多：短杆菌肽A与单个脂质之间的总相互作用能在0至-50千卡/摩尔之间变化。根据轨迹计算的脂质酰基链的氘四极分裂与实验数据吻合良好。与GA直接接触的脂质链是有序的，但由于蛋白质表面不规则，这种影响并不均匀。能量分解表明，脂质和蛋白质之间能量上最有利的相互作用涉及范德华力和静电相互作用的贡献几乎相等。位于本体-膜界面附近的色氨酸在介导与脂质甘油主链和水的氢键相互作用以及与烃链形成有利的范德华接触方面似乎特别重要。相比之下，同样位于界面附近的亮氨酸残基与脂质的相互作用主要是与烃脂质链的范德华相互作用。
