Center for Theoretical Biological Physics, Rice University, Houston, TX 77005.
Department of Chemistry, Rice University, Houston, TX 77005.
Proc Natl Acad Sci U S A. 2018 Sep 11;115(37):9234-9239. doi: 10.1073/pnas.1801406115. Epub 2018 Aug 27.
The presence of conflicting interactions, or frustration, determines how fast biomolecules can explore their configurational landscapes. Recent experiments have provided cases of systems with slow reconfiguration dynamics, perhaps arising from frustration. While it is well known that protein folding speed and mechanism are strongly affected by the protein native structure, it is still unknown how the response to frustration is modulated by the protein topology. We explore the effects of nonnative interactions in the reconfigurational and folding dynamics of proteins with different sizes and topologies. We find that structural correlations related to the folded state size and topology play an important role in determining the folding kinetics of proteins that otherwise have the same amount of nonnative interactions. In particular, we find that the reconfiguration dynamics of α-helical proteins are more susceptible to frustration than β-sheet proteins of the same size. Our results may explain recent experimental findings and suggest that attempts to measure the degree of frustration due to nonnative interactions might be more successful with α-helical proteins.
存在冲突的相互作用或干扰会决定生物分子在多大程度上能快速探索它们的构象景观。最近的实验提供了一些系统的例子，这些系统的重新配置动力学较慢，可能是由于干扰。虽然众所周知，蛋白质折叠的速度和机制受到蛋白质天然结构的强烈影响，但仍不清楚对干扰的反应是如何被蛋白质拓扑结构调节的。我们研究了不同大小和拓扑结构的蛋白质中非天然相互作用对重新配置和折叠动力学的影响。我们发现，与折叠状态大小和拓扑结构相关的结构相关性在确定具有相同数量非天然相互作用的蛋白质的折叠动力学方面起着重要作用。特别是，我们发现α-螺旋蛋白质的重新配置动力学比相同大小的β-折叠蛋白质更容易受到干扰。我们的研究结果可能解释了最近的实验发现，并表明尝试通过α-螺旋蛋白质测量由于非天然相互作用而产生的干扰程度可能会更加成功。
