Feller Scott E, Gawrisch Klaus, Woolf Thomas B
Department of Chemistry, Wabash College, 301 West Wabash, Crawfordsville, IN 47933, USA.
J Am Chem Soc. 2003 Apr 16;125(15):4434-5. doi: 10.1021/ja0345874.
An all-atom molecular dynamics simulation of rhodopsin in a membrane environment has been carried out with lipid composition similar to that of the retinal membrane. The initial conformation of the protein was taken from the X-ray crystallographic structure (1F88), while those of the lipids came from a previous molecular dynamics simulation. During the course of the 12.5 ns simulation, the initially randomly placed lipids adopt an anisotropic solvation structure around the protein. The lipids, having one saturated stearic acid chain and one polyunsaturated docosohexaenoic acid chain with a zwitterionic phosphatidylcholine headgroup, arrange themselves to maximize contact between the polyunsaturated chain and the protein surface. This organization is driven by energetically favorable interactions between the transmembrance helices and the docosohexaenoyl chains that are largely of the van der Waals type. These observations are consistent with various experimental studies on rhodopsin and other G-protein coupled receptors and with the picture of extreme flexibility in polyunsaturated fatty acid chains that has arisen from recent NMR and computational work.
已对视紫红质在膜环境中进行了全原子分子动力学模拟,其脂质组成与视网膜膜的脂质组成相似。蛋白质的初始构象取自X射线晶体学结构(1F88),而脂质的初始构象则来自先前的分子动力学模拟。在12.5纳秒的模拟过程中,最初随机放置的脂质在蛋白质周围形成了各向异性的溶剂化结构。这些脂质具有一条饱和硬脂酸链和一条带有两性离子磷脂酰胆碱头基团的多不饱和二十二碳六烯酸链,它们会自行排列,以使多不饱和链与蛋白质表面之间的接触最大化。这种排列是由跨膜螺旋与二十二碳六烯酰链之间在能量上有利的相互作用驱动的,这些相互作用主要是范德华力类型。这些观察结果与对视紫红质和其他G蛋白偶联受体的各种实验研究一致,也与最近核磁共振和计算研究中出现的多不饱和脂肪酸链具有极高灵活性的情况相符。