Local and macroscopic electrostatic interactions in single α-helices.
Local and macroscopic electrostatic interactions in single α-helices.
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DOI：
10.1038/nchembio.1739
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发表时间：
2015-03
影响因子：
14.8
通讯作者：
Woolfson DN
中科院分区：
文献类型：
--
作者：
Baker EG;Bartlett GJ;Crump MP;Sessions RB;Linden N;Faul CF;Woolfson DN
稳定蛋白质结构的非共价力尚未完全了解。解决这个问题的一种方法是研究肽中未折叠状态和α-螺旋之间的平衡。对于这些，静电力被认为是有贡献的，包括侧链之间的相互作用;主链和侧链;以及侧链和螺旋大偶极子。在这里，我们探测这些实验使用设计的肽。我们发现末端主链-侧链和某些侧链-侧链相互作用（即，邻近电荷之间的局部效应或原子间接触）比侧链-螺旋宏偶极静电对螺旋稳定性的贡献大得多，据信侧链-螺旋宏偶极静电在更大的距离下起作用。这对目前描述螺旋稳定性，理解蛋白质折叠，以及生物分子建模和模拟力场的改进都有影响。此外，它揭示了由单个α-螺旋形成的杆状结构的稳定性，这些结构在天然蛋白质（包括非肌肉肌球蛋白）中很常见。
The non-covalent forces that stabilise protein structures are not fully understood. One way to address this is to study equilibria between unfolded states and α-helices in peptides. For these, electrostatic forces are believed to contribute, including interactions between: side chains; the backbone and side chains; and side chains and the helix macrodipole. Here we probe these experimentally using designed peptides. We find that both terminal backbone-side chain and certain side chain-side chain interactions (i.e., local effects between proximal charges, or interatomic contacts) contribute much more to helix stability than side chain-helix macrodipole electrostatics, which are believed to operate at larger distances. This has implications for current descriptions of helix stability, understanding protein folding, and the refinement of force fields for biomolecular modelling and simulations. In addition, it sheds light on the stability of rod-like structures formed by single α-helices that are common in natural proteins including non-muscle myosins.