Department of Cell Biology and Biochemistry, Molecular and Translational Sciences, USAMRIID, Fredrick, Maryland.
Computational Sciences Division, U.S. Army Research Laboratory, Aberdeen Proving Ground, Maryland.
J Comput Chem. 2017 Jun 15;38(16):1342-1352. doi: 10.1002/jcc.24717. Epub 2017 Jan 28.
This work presents replica-exchange molecular dynamics simulations of inserting a 16-residue Ebola virus fusion peptide into a membrane bilayer. A computational approach is applied for modeling the peptide at the explicit all-atom level and the membrane-aqueous bilayer by a generalized Born continuum model with a smoothed switching function (GBSW). We provide an assessment of the model calculations in terms of three metrics: (1) the ability to reproduce the NMR structure of the peptide determined in the presence of SDS micelles and comparable structural data on other fusion peptides; (2) determination of the effects of the mutation Trp-8 to Ala and sequence discrimination of the homologous Marburg virus; and (3) calculation of potentials of mean force for estimating the partitioning free energy and their comparison to predictions from the Wimley-White interfacial hydrophobicity scale. We found the GBSW implicit membrane model to produce results of limited accuracy in conformational properties of the peptide when compared to the NMR structure, yet the model resolution is sufficient to determine the effect of sequence differentiation on peptide-membrane integration. © 2016 Wiley Periodicals, Inc.
这项工作提出了将 16 个残基的埃博拉病毒融合肽插入膜双层结构中的复制交换分子动力学模拟。应用计算方法在明确的全原子水平上对肽进行建模，并通过具有平滑切换函数 (GBSW) 的广义 Born 连续体模型对膜 - 水双层进行建模。我们根据三个指标评估模型计算：（1）在 SDS 胶束存在下复制确定的肽的 NMR 结构的能力，以及其他融合肽的可比结构数据；（2）测定突变色氨酸-8 到丙氨酸的影响和同源马尔堡病毒的序列鉴别；以及（3）计算平均力势以估计分配自由能，将其与 Wimley-White 界面疏水性标度的预测进行比较。我们发现，与 NMR 结构相比，GBSW 隐式膜模型在肽的构象性质上产生的结果准确性有限，但该模型的分辨率足以确定序列分化对肽 - 膜整合的影响。© 2016 Wiley Periodicals, Inc.
