论文标题
通过平行途径对单域蛋白的低力展开
Low force unfolding of a single-domain protein by parallel pathways
论文作者
论文摘要
在蛋白质展开速率对数的依赖性依赖性中，$ \ log k_u（f）$作为机械力的函数，$ f $，在单分子实验中可测量的偏差。特别是，作为$ f $的函数，$ \ log k_u（f）$中的向上曲率意味着基本的能量格局必须具有多维性，并且可能通过并行路径出现不断发展的可能性。在这里，使用野生型$β$ -Sandwich蛋白的SOP-SC模型和几个具有免疫球蛋白折叠的突变体的模拟，在展开的动力学中显示向上曲率。随着力的增加，过渡状态集成的结构发生了很大的变化，这表明了展开途径中的开关。我们的结果与以前的理论和实验研究结合在一起，表明可以从结构不相关的单个结构域蛋白的平行展开可以从$ \ log k_u（f）$的依赖性确定是力（或$ \ log k_u [c] $ [c] $ [c] $的函数，而不是浓度）。
Deviations from linearity in the dependence of the logarithm of protein unfolding rates, $\log k_u(f)$, as a function of mechanical force, $f$, measurable in single molecule experiments, can arise for many reasons. In particular, upward curvature in $\log k_u(f)$ as a function of $f$ implies that the underlying energy landscape must be multidimensional with the possibility that unfolding ensues by parallel pathways. Here, simulations using the SOP-SC model of a wild type $β$-sandwich protein and several mutants, with immunoglobulin folds, show upward curvature in the unfolding kinetics. There are substantial changes in the structures of the transition state ensembles as force is increased, signaling a switch in the unfolding pathways. Our results, when combined with previous theoretical and experimental studies, show that parallel unfolding of structurally unrelated single domain proteins can be determined from the dependence of $\log k_u(f)$ as a function of force (or $\log k_u[C]$ where $[C]$ is the denaturant concentration).
