Peripheral membrane proteins: Tying the knot between experiment and computation.
Peripheral membrane proteins: Tying the knot between experiment and computation.
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外周膜蛋白：连接实验和计算。
DOI：
10.1016/j.bbamem.2016.02.018
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发表时间：
2016
期刊：
影响因子：
--
通讯作者：
Klauda,JefferyB
中科院分区：
文献类型：
--
作者：
Monje-Galvan,Viviana;Klauda,JefferyB
实验生物学有助于回答关于系统的形态以及分子如何组织自己以维持健康的功能细胞的问题。单分子技术、光学和磁学实验以及荧光显微镜已经在多个尺度上探索结构和动力学信息方面取得了长足的进步。然而，有些细节只是太小了，或者过程太短暂，无法通过实验检测到。计算生物学提供了一座桥梁，可以在分子水平上理解实验结果，做出体内未曾见过的预测，并推动新的研究领域。本文综述了外周膜蛋白(PMPs)的研究进展，包括PMPs与膜的相互作用、在细胞生物学中的作用，以及为了更好地了解这些PMPs的结构和功能，实验和计算仍需克服的一些局限性。正如最近的许多评论所承认的那样，需要在实验和计算之间进行跨学科的努力，以便有有用的模型来引导未来对PMP的研究方向。我们介绍了一个关于PMP的案例研究的新结果，PMP作为一个复杂的机器控制细胞细胞器之间的脂类平衡，Osh4在酿酒酵母中。分子动力学模拟被用来检验蛋白质和膜模型之间的相互作用，这些模型反映了内质网和跨高尔基膜的脂质多样性。我们的研究与实验数据一致，实验数据显示，几个残基在稳定结合时(约200 ns进入轨道)与双层发生或小或大程度的相互作用。我们确定Phe 239是稳定蛋白质-膜相互作用的关键残基，以及蛋白质口腔区域的另外两个结合区域，即阿尔卑斯样基序和β6-β7环。本文是由J.C.Gumbart和Sergei Noskov编辑的题为：膜蛋白的特刊的一部分。
Experimental biology has contributed to answer questions about the morphology of a system and how molecules organize themselves to maintain a healthy functional cell. Single-molecule techniques, optical and magnetic experiments, and fluorescence microscopy have come a long way to probe structural and dynamical information at multiple scales. However, some details are simply too small or the processes are too short-lived to detect by experiments. Computational biology provides a bridge to understand experimental results at the molecular level, makes predictions that have not been seenin vivo, and motivates new fields of research. This review focuses on the advances on peripheral membrane proteins (PMPs) studies; what is known about their interaction with membranes, their role in cell biology, and some limitations that both experiment and computation still have to overcome to gain better structural and functional understanding of these PMPs. As many recent reviews have acknowledged, interdisciplinary efforts between experiment and computation are needed in order to have useful models that lead future directions in the study of PMPs. We present new results of a case study on a PMP that behaves as an intricate machine controlling lipid homeostasis between cellular organelles, Osh4 in yeastSaccharomyces cerevisiae. Molecular dynamics simulations were run to examine the interaction between the protein and membrane models that reflect the lipid diversity of the endoplasmic reticulum and trans-Golgi membranes. Our study is consistent with experimental data showing several residues that interact to smaller or larger extent with the bilayer upon stable binding (~ 200 ns into the trajectory). We identified PHE239 as a key residue stabilizing the protein–membrane interaction along with two other binding regions, the ALPS-like motif and the β6–β7 loops in the mouth region of the protein. This article is part of a Special Issue entitled: Membrane Proteins edited by J.C. Gumbart and Sergei Noskov.
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影响因子：
3.3
作者：
Klauda, Jeffery B.;Venable, Richard M.;Freites, J. Alfredo;O'Connor, Joseph W.;Tobias, Douglas J.;Mondragon-Ramirez, Carlos;Vorobyov, Igor;MacKerell, Alexander D., Jr.;Pastor, Richard W.
通讯作者：
Pastor, Richard W.
影响因子：
3.4
作者：
Stahelin RV;Scott JL;Frick CT
通讯作者：
Frick CT
DOI：
--
发表时间：
2014
期刊：
影响因子：
--
作者：
M. Kalani;E. Tajkhorshid
通讯作者：
E. Tajkhorshid
囊泡结合和磷脂动力学与磷脂酶 C 活性的相关性
影响因子：
4.8
作者：
Mingming Pu;X.;A. Redfield;A. Gershenson;M. Roberts
通讯作者：
M. Roberts
细胞生物学：脂质流的逆流
影响因子：
64.8
作者：
A. Menon;T. Levine
通讯作者：
T. Levine