Department of Physics and the Institute for Complex Adaptive Matter, University of California at Davis, Davis, California 95616, USA.
Proteins. 2012 May;80(5):1299-307. doi: 10.1002/prot.24026. Epub 2012 Feb 13.
We employ all-atom structure-based models with a force field with multiple energetic basins for the C-terminal (residues 166-226) of the mammalian prion protein. One basin represents the known alpha-helical (αH) structure while the other represents the same residues in a left-handed beta-helical (LHBH) conformation. The LHBH structure has been proposed to help describe one class of in vitro grown fibrils, as well as possibly self-templating the conversion of normal cellular prion protein to the infectious form. Yet, it is unclear how the protein may make this global rearrangement. Our results demonstrate that the conformation changes are not strongly limited by large-scale geometry modification and that there may exist an overall preference for the LHBH conformation. Furthermore, our model presents novel intermediate trapping conformations with twisted LHBH structure.
我们采用基于全原子结构的模型和具有多个能量基态的力场来研究哺乳动物朊病毒蛋白的 C 末端（残基 166-226）。一个基态代表已知的α螺旋（αH）结构，另一个基态代表相同残基的左手β螺旋（LHBH）构象。LHBH 结构被提出有助于描述一类体外生长的纤维，也可能自我模板化将正常细胞朊病毒蛋白转化为感染形式。然而，目前尚不清楚蛋白质如何实现这种全局重排。我们的研究结果表明，构象变化不受大规模几何修饰的强烈限制，并且可能存在对 LHBH 构象的整体偏好。此外，我们的模型提出了具有扭曲 LHBH 结构的新型中间捕获构象。
