An ensemble dynamics approach to decipher solid-state NMR observables of membrane proteins
An ensemble dynamics approach to decipher solid-state NMR observables of membrane proteins
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DOI：
10.1016/j.bbamem.2011.07.048
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发表时间：
2012-02-01
影响因子：
3.4
通讯作者：
Kim, Taehoon
中科院分区：
文献类型：
--
作者：
Im, Wonpil;Jo, Sunhwan;Kim, Taehoon
固体核磁共振（SSNMR）是测定膜蛋白和多肽在脂双层中取向的重要工具。这种取向描述提供了关于膜蛋白功能的基本信息。然而，当一个半静态的单一构象模型被用来解释各种SSNMR观测值，重要的动力学信息可能会丢失，有时，甚至取向信息可能会被误解。此外，在过去的十年中，分子动力学（MD）模拟和半静态SSNMR解释显示出一定程度的跨膜螺旋方向和动力学方面的差异。最近提出了动态拟合模型，以解决这些差异，考虑到跨膜螺旋全身运动使用额外的参数。作为一种替代方法，我们已经开发了SSNMR系综动力学（SSNMR-ED）使用多个构象模型，它产生的结构，满足实验观测值没有任何拟合参数的系综。在这篇综述中，各种计算方法来确定跨膜螺旋的方向进行了讨论，VpuTM（从HIV-1）和WALP 23（一种合成肽）的分布从SSNMR-ED模拟比较从MD模拟和半静态/动态拟合模型。这样的比较说明，SSNMR-ED可以用作从SSNMR测量中提取膜蛋白结构和动力学的一般手段。这篇文章是一个特殊问题的一部分，题为：膜蛋白的结构和功能。(C)2011 Elsevier B. V.保留所有权利。
Solid-state NMR (SSNMR) is an invaluable tool for determining orientations of membrane proteins and peptides in lipid bilayers. Such orientational descriptions provide essential information about membrane protein functions. However, when a semi-static single conformer model is used to interpret various SSNMR observables, important dynamics information can be missing, and, sometimes, even orientational information can be misinterpreted. In addition, over the last decade, molecular dynamics (MD) simulation and semi-static SSNMR interpretation have shown certain levels of discrepancies in terms of transmembrane helix orientation and dynamics. Dynamic fitting models have recently been proposed to resolve these discrepancies by taking into account transmembrane helix whole body motions using additional parameters. As an alternative approach, we have developed SSNMR ensemble dynamics (SSNMR-ED) using multiple conformer models, which generates an ensemble of structures that satisfies the experimental observables without any fitting parameters. In this review, various computational methods for determining transmembrane helix orientations are discussed, and the distributions of VpuTM (from HIV-1) and WALP23 (a synthetic peptide) orientations from SSNMR-ED simulations are compared with those from MD simulations and semi-static/dynamic fitting models. Such comparisons illustrate that SSNMR-ED can be used as a general means to extract both membrane protein structure and dynamics from the SSNMR measurements. This article is part of a Special Issue entitled: Membrane protein structure and function. (C) 2011 Elsevier B.V. All rights reserved.