Department of Physics, North Carolina State University , Raleigh, North Carolina 27695, United States.
J Phys Chem B. 2014 Jan 9;118(1):69-80. doi: 10.1021/jp409355r. Epub 2013 Dec 20.
We report on extensive molecular dynamics (MD) simulations of the tridecapeptide corresponding to residues 659-671 of the envelope glycoprotein gp41 of HIV-1, which spans the 2F5 monoclonal antibody epitope ELDKWA. Previously, X-ray crystallography, nuclear magnetic resonance, and circular dichroism experiments have yielded conflicting conformational information, but there is a growing consensus that the monomeric peptide in aqueous solution is disordered. Here, we use the latest, state-of-the-art AMBER force fields to describe the complex conformational landscape of gp41(659-671). We have analyzed the conformational ensembles of the peptide in solution both without applied restraints and under successive tensile restraints. In contrast to previous MD simulations, our results are consistent with the bulk of the experimental findings. The amount of helical population is important in aqueous solution, but this structure forms part of a flexible conformational ensemble with a rugged free energy landscape with shallow minima. Under uniaxial tension, the disordered peptide first becomes fully helical before melting into turns, loops, and 310-helices. The conformational ensemble includes epitope conformations close to an NMR solution structure (PDB ID 1LCX ) as well as epitope conformations close to a very different, extended crystal structure (PDB ID 1TJH ).
我们报告了对 HIV-1 包膜糖蛋白 gp41 第 659-671 位残基对应的十三肽的广泛分子动力学（MD）模拟，该肽跨越了 2F5 单克隆抗体表位ELDKWA。以前，X 射线晶体学、核磁共振和圆二色性实验得出了相互矛盾的构象信息，但越来越多的共识认为单体肽在水溶液中是无序的。在这里，我们使用最新的、最先进的 AMBER 力场来描述 gp41（659-671）的复杂构象景观。我们分析了在没有施加约束和在连续拉伸约束下溶液中肽的构象集合。与以前的 MD 模拟相比，我们的结果与大量的实验结果一致。螺旋体的数量在水溶液中很重要，但这种结构是具有粗糙自由能景观的灵活构象集合的一部分，其中有浅的极小值。在单轴拉伸下，无序肽首先完全变成螺旋，然后再变成转角、环和 310 螺旋。构象集合包括接近 NMR 溶液结构（PDB ID 1LCX）的表位构象，以及接近非常不同的伸展晶体结构（PDB ID 1TJH）的表位构象。
