Structure of gramicidin A in a lipid bilayer environment determined using molecular dynamics simulations and solid-state NMR data
Structure of gramicidin A in a lipid bilayer environment determined using molecular dynamics simulations and solid-state NMR data
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DOI：
10.1021/ja029317k
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发表时间：
2003-08-13
影响因子：
15
通讯作者：
Roux, B
中科院分区：
文献类型：
--
作者：
Allen, TW;Andersen, OS;Roux, B
最近已经针对跨膜grannicidin A通道提出了两种不同的高分辨率结构：一种基于定向磷脂双层中的固态NMR实验（Ketchem，R.的R.; Roux，B.;克罗斯，T。A. Structure 1997，5，1655-1669; Protein Data Bank，PDB：1 MAG）;和一种基于洗涤剂胶束中的二维NMR（Townsley，L. E.的;塔克，W。一、Sham，S.;欣顿，J.F. Biochemistry 2001，40，11676-11686; PDB：1JNO）。尽管总体协议，这两种结构不同的peparticle骨干间距和几个侧链的方向，特别是在位置9的色氨酸。鉴于肽的骨干和色氨酸侧链的离子渗透的重要性，我们进行了调查的两种结构，使用分子动力学模拟与明确的脂质双层膜，类似于用于固态NMR实验的系统。基于0.1亩的模拟，这两个骨干结构收敛到一个结构与6.25残基每转，在协议与X-射线散射，并广泛的协议与SS骨干NMR观测。Trp 9的侧链是移动的，比Trp 11、13和15更易移动，并且在1 JNO和1 MAG中的取向之间进行自发转变。根据经验拟合的NMR结果，伞采样计算，我们得出结论，行程9花费80%的时间在1 JNO方向和20%的1 MAG方向。这些结果强调了利用分子动力学模拟的分析和解释的结构信息从固态NMR。
Two different high-resolution structures recently have been proposed for the membrane-spanning grannicidin A channel: one based on solid-state NMR experiments in oriented phospholipid bilayers (Ketchem, R. R.; Roux, B.; Cross, T. A. Structure 1997, 5, 1655-1669; Protein Data Bank, PDB:1MAG); and one based on two-dimensional NMR in detergent micelles (Townsley, L. E.; Tucker, W. A.; Sham, S.; Hinton, J. F. Biochemistry 2001, 40, 11676-11686; PDB:1JNO). Despite overall agreement, the two structures differ in pepticle backbone pitch and the orientation of several side chains; in particular that of the Trp at position 9. Given the importance of the peptide backbone and Trp side chains for ion permeation, we undertook an investigation of the two structures using molecular dynamics simulation with an explicit lipid bilayer membrane, similar to the system used for the solid-state NMR experiments. Based on 0.1 mus of simulation, both backbone structures converge to a structure with 6.25 residues per turn, in agreement with X-ray scattering, and broad agreement with SS backbone NMR observables. The side chain of Trp 9 is mobile, more so than Trp 11, 13, and 15, and undergoes spontaneous transitions between the orientations in 1JNO and 1MAG. Based on empirical fitting to the NMR results, and umbrella sampling calculations, we conclude that Trip 9 spends 80% of the time in the 1JNO orientation and 20% in the 1 MAG orientation. These results underscore the utility of molecular dynamics simulations in the analysis and interpretation of structural information from solid-state NMR.