Conformational sampling and dynamics of membrane proteins from 10-nanosecond computer simulations
Conformational sampling and dynamics of membrane proteins from 10-nanosecond computer simulations
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DOI：
10.1002/prot.20257
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发表时间：
2004-12-01
影响因子：
2.9
通讯作者：
Sansom, MSP
中科院分区：
文献类型：
--
作者：
Faraldo-Gómez, JD;Forrest, LR;Sansom, MSP
在当前的报告中，我们提供了在分子动力学模拟10纳秒量级的膜蛋白中完成的构象空间采样的收敛的定量分析。一组不同大小和拓扑的蛋白质被考虑在内，从螺旋状的毛孔，如革兰西丁和小的β-桶，如OmpT，到更大和更复杂的结构，如视紫红质和FepA。C-α原子轨迹的主成分分析被用来评估构象采样在跨膜区和整个蛋白质中的收敛，而平均结构的时间依赖性被分析以获得单域信息。膜包埋区，特别是那些小的或结构简单的蛋白质，被发现实现了合理的收敛。相比之下，缺乏二级结构的膜外域往往明显采样不足，表现出连续的结构漂移。这种漂移导致计算的B因子有很大的不精确度，这与实验数据的任何定量比较都是有偏差的。鉴于这样的局限性，我们建议类似的分析在膜蛋白动力学的模拟研究中可能是有价值的，以便对任何与生物学相关的观察结果赋予一定程度的置信度。(C)2004年Wiley-Liss公司
In the current report, we provide a quantitative analysis of the convergence of the sampling of conformational space accomplished in molecular dynamics simulations of membrane proteins of duration in the order of 10 nanoseconds. A set of proteins of diverse size and topology is considered, ranging from helical pores such as gramicidin and small beta-barrels such as OmpT, to larger and more complex structures such as rhodopsin and FepA. Principal component analysis of the C-alpha-atom trajectories was employed to assess the convergence of the conformational sampling in both the transmembrane domains and the whole proteins, while the time-dependence of the average structure was analyzed to obtain single-domain information. The membrane-embedded regions, particularly those of small or structurally simple proteins, were found to achieve reasonable convergence. By contrast, extra-membranous domains lacking secondary structure are often markedly under-sampled, exhibiting a continuous structural drift. This drift results in a significant imprecision in the calculated B-factors, which detracts from any quantitative comparison to experimental data. In view of such limitations, we suggest that similar analyses may be valuable in simulation studies of membrane protein dynamics, in order to attach a level of confidence to any biologically relevant observations. (C) 2004 Wiley-Liss, Inc.