Putzu Marina, Kara Sezgin, Afonin Sergii, Grage Stephan L, Bordessa Andrea, Chaume Grégory, Brigaud Thierry, Ulrich Anne S, Kubař Tomáš
Center for Functional Nanostructures and Institute of Physical Chemistry, Karlsruhe Institute of Technology, Karlsruhe, Germany.
Institute of Organic Chemistry, Karlsruhe Institute of Technology, Karlsruhe, Germany.
Biophys J. 2017 Jun 20;112(12):2602-2614. doi: 10.1016/j.bpj.2017.05.019.
Microsecond molecular dynamics simulations of harzianin HK VI (HZ) interacting with a dimyristoylphosphatidylcholine bilayer were performed at the condition of low peptide-to-lipid ratio. Two orientations of HZ molecule in the bilayer were found and characterized. In the orientation perpendicular to the bilayer surface, HZ induces a local thinning of the bilayer. When inserted into the bilayer parallel to its surface, HZ is located nearly completely within the hydrophobic region of the bilayer. A combination of solid-state NMR and circular dichroism experiments found the latter orientation to be dominant. An extended sampling simulation provided qualitative results and showed the same orientation to be a global minimum of free energy. The secondary structure of HZ was characterized, and it was found to be located in the 3-helical family. The specific challenges of computer simulation of nonpolar peptides are discussed briefly.
在低肽脂比条件下，对哈茨菌素HK VI（HZ）与二肉豆蔻酰磷脂酰胆碱双层相互作用进行了微秒级分子动力学模拟。发现并表征了HZ分子在双层中的两种取向。在垂直于双层表面的取向中，HZ会导致双层局部变薄。当平行于双层表面插入时，HZ几乎完全位于双层的疏水区域内。固态核磁共振和圆二色性实验相结合发现后一种取向占主导。扩展采样模拟给出了定性结果，并表明该取向是自由能的全局最小值。对HZ的二级结构进行了表征，发现它属于3 - 螺旋家族。简要讨论了非极性肽计算机模拟的具体挑战。
