Department of Chemistry, State University of New York at Stony Brook, Stony Brook, New York 11794, United States.
J Phys Chem B. 2012 May 3;116(17):5152-9. doi: 10.1021/jp212132v. Epub 2012 Apr 20.
Configuration-dependent diffusion (CDD) is important for protein folding kinetics with small thermodynamic barriers. CDD can be even more crucial in downhill folding without thermodynamic barriers. We explored the CDD of a downhill protein (BBL), and a two-state protein (CI2). The hidden kinetic barriers due to CDD were revealed. The increased ~1 k(B)T kinetic barrier is in line with experimental value based on other fast folding proteins. Compared to that of CI2, the effective free-energy profile of BBL is found to be significantly influenced by CDD, and the kinetics are totally determined by diffusion. These findings are consistent with both earlier bulk and single-molecule fluorescence measurements. In addition, we found the temperature dependence of CDD. We also found that the ratio of folding transition temperature against optimal kinetic folding temperature can provide both a quantitative measure for the underlying landscape topography and an indicator for the possible appearance of downhill folding. Our study can help for a better understanding of the role of diffusion in protein folding dynamics.
构象相关扩散（CDD）对于具有小热力学势垒的蛋白质折叠动力学很重要。在没有热力学势垒的下坡折叠中，CDD 甚至可能更为关键。我们研究了一种下坡蛋白（BBL）和一种两态蛋白（CI2）的 CDD。揭示了由于 CDD 导致的隐藏动力学势垒。增加的约 1 k(B)T 动力学势垒与基于其他快速折叠蛋白的实验值一致。与 CI2 相比，BBL 的有效自由能分布受到 CDD 的显著影响，动力学完全由扩散决定。这些发现与早期的体相和单分子荧光测量结果一致。此外，我们还发现了 CDD 的温度依赖性。我们还发现，折叠转变温度与最佳动力学折叠温度的比值可以提供对基础景观地形的定量衡量，并指示可能出现下坡折叠的情况。我们的研究有助于更好地理解扩散在蛋白质折叠动力学中的作用。
