Department of Chemistry, Michigan State University, East Lansing, Michigan 48824, USA.
J Phys Chem B. 2010 Jan 28;114(3):1407-16. doi: 10.1021/jp907366g.
Influenza fusion peptide is critical for mediating the fusion of viral and host cell membranes during viral entry. The interaction of monomeric influenza fusion peptide with membranes is studied with replica exchange molecular dynamics simulations using a new implicit membrane model to effectively reach microsecond to millisecond time scales. The conformational sampling of the fusion peptide was studied as a function of different N- and C-termini, including an experimental construct with an additional C-terminal tag, as well as a function of protonation of acidic residues. It is found that the influenza fusion peptide mostly adopts helical structures with a pronounced kink at residues 11-13 with both N-terminal and C-terminal helices oriented mostly parallel to the membrane surface. A charged C-terminus and the presence of a charge C-terminal tag significantly alters the conformational sampling of the fusion peptide and results in more diverse conformational ensembles that include obliquely inserted N-terminal peptide structures. Protonation of acidic residues also affects the conformational sampling, however, based on pK(a) shift estimates the overall effect of pH = 5 on the conformational sampling of the influenza fusion peptide appears to be only minor.
流感融合肽在介导病毒进入宿主细胞时病毒和宿主细胞膜的融合中起关键作用。使用新的隐式膜模型的 replica 交换分子动力学模拟研究了单体流感融合肽与膜的相互作用，以有效地达到微秒到毫秒的时间尺度。研究了融合肽的构象采样作为不同 N-和 C-末端的函数，包括带有额外 C-末端标记的实验构建体，以及酸性残基质子化的函数。结果发现，流感融合肽主要采用带有明显 11-13 位残基扭曲的螺旋结构，N-末端和 C-末端螺旋大多与膜表面平行。带电荷的 C-末端和 C-末端标记的存在显著改变了融合肽的构象采样，导致包括斜插入的 N-末端肽结构在内的更多样化的构象集合。酸性残基的质子化也会影响构象采样，但是，根据 pK(a) 位移估计，pH=5 对流感融合肽构象采样的总体影响似乎很小。
