Transferring the PRIMO Coarse-Grained Force Field to the Membrane Environment: Simulations of Membrane Proteins and Helix-Helix Association.
Transferring the PRIMO Coarse-Grained Force Field to the Membrane Environment: Simulations of Membrane Proteins and Helix-Helix Association.
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DOI：
10.1021/ct500443v
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发表时间：
2014-08-12
影响因子：
5.5
通讯作者：
Feig, Michael
中科院分区：
文献类型：
--
作者：
Kar, Parimal;Gopal, Srinivasa Murthy;Cheng, Yi-Ming;Panahi, Afra;Feig, Michael
描述了最近开发的PRIMO粗粒度力场在膜环境中的扩展，PRIMO- m。膜环境采用非均匀介质广义Born （HDGB）方法建模，该方法简单地取代了PRIMO中的标准广义Born模型，无需进一步参数化。通过比较氨基酸插入自由能谱和在膜蛋白和膜相互作用肽分子动力学模拟中的应用，验证了模型的有效性。含有148-661个氨基酸的膜蛋白在大多数系统中显示稳定的均方根偏差（RMSD）在2到4 Å之间。跨膜螺旋肽保持螺旋形状，并表现出倾斜角度与实验或其他模拟数据很好地一致。利用复制交换分子动力学模拟模拟了两个糖蛋白A （GpA）螺旋的结合，得到了具有交叉角的正确二聚体结构，与先前的研究一致。最后，流感融合肽的构象采样也产生与先前研究一致的结构。总之，这些发现表明PRIMO- m可以用于研究膜结合肽和蛋白质，并验证了PRIMO粗粒度力场的可转移性。
An extension of the recently developed PRIMO coarse-grained force field to membrane environments, PRIMO-M, is described. The membrane environment is modeled with the heterogeneous dielectric generalized Born (HDGB) methodology that simply replaces the standard generalized Born model in PRIMO without further parametrization. The resulting model was validated by comparing amino acid insertion free energy profiles and application in molecular dynamics simulations of membrane proteins and membrane-interacting peptides. Membrane proteins with 148–661 amino acids show stable root-mean-squared-deviations (RMSD) between 2 and 4 Å for most systems. Transmembrane helical peptides maintain helical shape and exhibit tilt angles in good agreement with experimental or other simulation data. The association of two glycophorin A (GpA) helices was simulated using replica exchange molecular dynamics simulations yielding the correct dimer structure with a crossing angle in agreement with previous studies. Finally, conformational sampling of the influenza fusion peptide also generates structures in agreement with previous studies. Overall, these findings suggest that PRIMO-M can be used to study membrane bound peptides and proteins and validates the transferable nature of the PRIMO coarse-grained force field.
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影响因子：
2.9
作者：
Gopal, Srinivasa M.;Mukherjee, Shayantani;Cheng, Yi-Ming;Feig, Michael
通讯作者：
Feig, Michael
影响因子：
3.4
作者：
Bu, Lintao;Im, Wonpil;Brooks, Charles L., III
通讯作者：
Brooks, Charles L., III
影响因子：
15
作者：
Hénin, J;Pohorille, A;Chipot, C
通讯作者：
Chipot, C
影响因子：
4.4
作者：
Friedel, M;Shea, JE
通讯作者：
Shea, JE
影响因子：
15
作者：
Bond PJ;Sansom MS
通讯作者：
Sansom MS