Dolenc Jožica, Meier Beat H, Rusu Victor H, van Gunsteren Wilfred F
Laboratory of Physical Chemistry, Swiss Federal Institute of Technology, ETH, Vladimir-Prelog-Weg 2, 8093 Zurich, Switzerland.
Phys Chem Chem Phys. 2016 Feb 17;18(8):5860-6. doi: 10.1039/c6cp00057f.
The structural variability of a 16-residue loop (residues 246-261) which is in part disordered and connects two layers of the β-solenoid formed by the prion-form of HET-s and its prion domain HET-s(218-289) is investigated using molecular dynamics computer simulation. A system of three HET-s(218-289) molecules in a β-sheet structure as in the fibril is simulated in aqueous solution. The trajectory structures appear to be consistent with the Cα chemical shift data obtained. In order to delineate the influence of the β-sheet core of the fibril upon the structural variability of the loop, the latter is also simulated without the β-sheet core, but with its N- and C-terminal residues restrained at their positions in the fibril. The analysis of the trajectories shows that the structural variability of the loop is restricted by the β-sheet core, least at its N-terminal end and most in the middle of the trimer.
利用分子动力学计算机模拟研究了一个16个残基的环（残基246 - 261）的结构变异性，该环部分无序，连接由HET-s的朊病毒形式及其朊病毒结构域HET-s(218 - 289)形成的β-螺线管的两层。模拟了一个在水溶液中处于β-折叠结构的三个HET-s(218 - 289)分子的体系，如同在原纤维中一样。轨迹结构似乎与所获得的Cα化学位移数据一致。为了描述原纤维的β-折叠核心对环结构变异性的影响，还在没有β-折叠核心的情况下对环进行了模拟，但将其N端和C端残基限制在原纤维中的位置。轨迹分析表明，环的结构变异性受到β-折叠核心的限制，在其N端限制最小，在三聚体中间限制最大。
