Woolf T B, Roux B
Department of Chemistry, Université de Montréal, PQ Canada.
Proc Natl Acad Sci U S A. 1994 Nov 22;91(24):11631-5. doi: 10.1073/pnas.91.24.11631.
A molecular dynamics simulation of the gramicidin A channel in an explicit dimyristoyl phosphatidylcholine bilayer was generated to study the details of lipid-protein interactions at the microscopic level. Solid-state NMR properties of the channel averaged over the 500-psec trajectory are in excellent agreement with available experimental data. In contrast with the assumptions of macroscopic models, the membrane/solution interface region is found to be at least 12 A thick. The tryptophan side chains, located within the interface, are found to form hydrogen bonds with the ester carbonyl groups of the lipids and with water, suggesting their important contribution to the stability of membrane proteins. Individual lipid-protein interactions are seen to vary from near 0 to -50 kcal/mol. The most strongly interacting conformations are short-lived and have a nearly equal contribution from both van der Waals and electrostatic energies. This approach for performing molecular dynamics simulations of membrane proteins in explicit phospholipid bilayers should help in studying the structure, dynamics, and energetics of lipid-protein interactions.
为了在微观层面研究脂质 - 蛋白质相互作用的细节，我们对存在于明确的二肉豆蔻酰磷脂酰胆碱双层膜中的短杆菌肽A通道进行了分子动力学模拟。在500皮秒轨迹上对通道进行平均后的固态核磁共振特性与现有实验数据高度吻合。与宏观模型的假设相反，发现膜/溶液界面区域至少有12埃厚。位于界面内的色氨酸侧链与脂质的酯羰基以及水形成氢键，这表明它们对膜蛋白的稳定性有重要贡献。单个脂质 - 蛋白质相互作用的能量从接近0到 -50千卡/摩尔不等。相互作用最强的构象寿命较短，范德华力和静电能的贡献几乎相等。这种在明确的磷脂双层膜中对膜蛋白进行分子动力学模拟的方法，应有助于研究脂质 - 蛋白质相互作用的结构、动力学和能量学。
