Indole localization in lipid membranes revealed by molecular simulation
Indole localization in lipid membranes revealed by molecular simulation
复制标题
DOI：
10.1529/biophysj.105.080275
复制
发表时间：
2006-09-01
影响因子：
3.4
通讯作者：
Nymeyer, Hugh
中科院分区：
文献类型：
--
作者：
Norman, Kristen E.;Nymeyer, Hugh
众所周知，氨基酸残基色氨酸及其侧链类似物，如吲哚，被脂质双分子层的界面区域强烈吸引。苯丙氨酸及其侧链类似物，如苯，不局限于界面，而是分布在整个脂质双分子层。我们使用分子动力学研究了吲哚和苯在POPC双层结构中的定位和取向的细节，以及导致它们不同性质的因素。我们确定了双分子层中吲哚定位的三个位点：1)，靠近甘油部分的界面位点；2)界面上靠近胆碱部分的弱结合位点；3)双分子层碳氢化合物核心中心的弱结合位点。苯同样位于三个位置，但最稳定的位置是烃核，其次是甘油部分附近的位置。吲哚从水中向碳氢化合物核心的转移表现出典型的疏水效应。相反，界面结合是强烈的焓驱动的。我们用几种不同的部分电荷来研究影响吲哚和苯的取向和空间分布的因素。我们的模拟表明，许多静电相互作用似乎有助于定位，包括与脂质羰基的氢键，阳离子-p相互作用，吲哚偶极子与脂质双分子层的强界面电场之间的相互作用，以及由于非极性力和局部电介质在双分子层中的位置变化不匹配而导致的非特异性静电稳定。
It is commonly known that the amino acid residue tryptophan and its side-chain analogs, e. g., indole, are strongly attracted to the interfacial region of lipid bilayers. Phenylalanine and its side-chain analogs, e. g., benzene, do not localize in the interface but are distributed throughout the lipid bilayer. We use molecular dynamics to investigate the details of indole and benzene localization and orientation within a POPC bilayer and the factors that lead to their different properties. We identify three sites in the bilayer at which indole is localized: 1), a site in the interface near the glycerol moiety; 2), a weakly bound site in the interface near the choline moiety; and 3), a weakly bound site in the center of the bilayer's hydrocarbon core. Benzene is localized in the same three positions, but the most stable position is the hydrocarbon core followed by the site near the glycerol moiety. Transfer of indole from water to the hydrocarbon core shows a classic hydrophobic effect. In contrast, interfacial binding is strongly enthalpy driven. We use several different sets of partial charges to investigate the factors that contribute to indole's and benzene's orientational and spatial distribution. Our simulations show that a number of electrostatic interactions appear to contribute to localization, including hydrogen bonding to the lipid carbonyl groups, cation-p interactions, interactions between the indole dipole and the lipid bilayer's strong interfacial electric field, and nonspecific electrostatic stabilization due to a mismatch in the variation of the nonpolar forces and local dielectric with position in the bilayer.