MemProtMD: Automated Insertion of Membrane Protein Structures into Explicit Lipid Membranes.
MemProtMD: Automated Insertion of Membrane Protein Structures into Explicit Lipid Membranes.
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DOI：
10.1016/j.str.2015.05.006
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发表时间：
2015-07-07
期刊：
影响因子：
--
通讯作者：
Sansom MS
中科院分区：
文献类型：
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作者：
Stansfeld PJ;Goose JE;Caffrey M;Carpenter EP;Parker JL;Newstead S;Sansom MS
已确定的膜蛋白结构的数量呈指数增长。然而，这些结构通常在不存在其脂质环境的情况下被解析。粗粒分子动力学（CGMD）模拟使膜蛋白插入到明确的模型脂质双层。我们已经实现了CGMD方法的自动化，使膜蛋白结构能够在释放到PDB中并嵌入膜中时被识别。模拟分析蛋白质-脂质相互作用，识别脂质结合位点，并揭示局部双层变形加上膜内的分子通路。膜蛋白/双层复合物的粗粒度模型被转换为原子级分辨率，以便进一步分析和模拟。使用这种自动化的模拟管道，我们分析了一些最近确定的膜蛋白结构，以预测它们在膜内的位置，它们的脂质/蛋白质相互作用，以及增强对每种蛋白质局部膜环境的理解的功能意义。一个模拟管道预测的位置膜蛋白在一个双分子层一个协议，用于确定新的膜蛋白结构在PDB的脂质结合位点的分析和局部双层变形的膜蛋白功能的影响，从增强了解当地的膜环境Stansfeld等。MemProtMD是一个自动化的分子模拟管道，用于将膜蛋白结构插入到明确的脂质双层膜中。所有已知的膜蛋白结构的模拟分析揭示了蛋白质诱导的膜变形的细节和残留物分布的规则，并有利于细化膜蛋白。
There has been exponential growth in the number of membrane protein structures determined. Nevertheless, these structures are usually resolved in the absence of their lipid environment. Coarse-grained molecular dynamics (CGMD) simulations enable insertion of membrane proteins into explicit models of lipid bilayers. We have automated the CGMD methodology, enabling membrane protein structures to be identified upon their release into the PDB and embedded into a membrane. The simulations are analyzed for protein-lipid interactions, identifying lipid binding sites, and revealing local bilayer deformations plus molecular access pathways within the membrane. The coarse-grained models of membrane protein/bilayer complexes are transformed to atomistic resolution for further analysis and simulation. Using this automated simulation pipeline, we have analyzed a number of recently determined membrane protein structures to predict their locations within a membrane, their lipid/protein interactions, and the functional implications of an enhanced understanding of the local membrane environment of each protein. A simulation pipeline for predicting the location of a membrane protein in a bilayer A protocol for identifying novel membrane protein structures in the PDB Analysis of lipid binding sites and local bilayer deformation by membrane proteins Functional implications from enhanced understanding of local membrane environments Stansfeld et al. present MemProtMD, an automated pipeline for molecular simulations to insert membrane protein structures into explicit lipid bilayer membranes. An analysis of simulations of all known membrane protein structures reveals details of protein-induced membrane deformation and rules for residue distribution, and facilitates refinement of membrane proteins.