Yang Wei Yuan, Gruebele Martin
Center for Biophysics and Computational Biology, University of Illinois, Urbana Illinois 61801, USA.
Nature. 2003 May 8;423(6936):193-7. doi: 10.1038/nature01609.
Many small proteins seem to fold by a simple process explicable by conventional chemical kinetics and transition-state theory. This assumes an instant equilibrium between reactants and a high-energy activated state. In reality, equilibration occurs on timescales dependent on the molecules involved, below which such analyses break down. The molecular timescale, normally too short to be seen in experiments, can be of a significant length for proteins. To probe it directly, we studied very rapidly folding mutants of the five-helix bundle protein lambda(6-85), whose activated state is significantly populated during folding. A time-dependent rate coefficient below 2 micro s signals the onset of the molecular timescale, and hence the ultimate speed limit for folding. A simple model shows that the molecular timescale represents the natural pre-factor for transition state models of folding.
许多小蛋白质似乎通过一个能用传统化学动力学和过渡态理论解释的简单过程进行折叠。这假定反应物与高能活化态之间存在瞬间平衡。实际上，平衡是在取决于所涉及分子的时间尺度上发生的，低于这个时间尺度，此类分析就会失效。分子时间尺度通常太短，在实验中无法观察到，但对于蛋白质来说可能相当长。为了直接探究它，我们研究了五螺旋束蛋白λ(6 - 85)的快速折叠突变体，其活化态在折叠过程中大量存在。低于2微秒的时间依赖性速率系数标志着分子时间尺度的开始，因此也是折叠的最终速度极限。一个简单模型表明，分子时间尺度代表了折叠过渡态模型的自然前置因子。
