Rhodopsin exhibits a preference for solvation by polyunsaturated docosohexaenoic acid
Rhodopsin exhibits a preference for solvation by polyunsaturated docosohexaenoic acid
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DOI：
10.1021/ja0345874
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发表时间：
2003-04-16
影响因子：
15
通讯作者：
Woolf, TB
中科院分区：
文献类型：
--
作者：
Feller, SE;Gawrisch, K;Woolf, TB
用全原子分子动力学方法模拟了视紫红质在膜环境中的分子动力学行为，其脂质组成与视网膜膜相似。蛋白质的初始构象来自X射线晶体结构（1F88），而脂质的初始构象来自先前的分子动力学模拟。在12.5 ns模拟过程中，最初随机放置的脂质在蛋白质周围采用各向异性溶剂化结构。具有一个饱和硬脂酸链和一个具有两性离子磷脂酰胆碱头基的多不饱和二十二碳六烯酸链的脂质自身排列以使多不饱和链与蛋白质表面之间的接触最大化。这种组织是由跨膜螺旋和二十二碳六烯酰基链（主要是货车德瓦尔斯型）之间的有利相互作用驱动的。这些观察结果与视紫红质和其他G蛋白偶联受体的各种实验研究一致，并且与最近的NMR和计算工作中出现的多不饱和脂肪酸链的极端灵活性的图片一致。
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.