Zhuang Zhuoyun, Jewett Andrew I, Soto Patricia, Shea Joan-Emma
Department of Chemistry and Biochemistry, University of California, Santa Barbara, CA 93106-9510, USA.
Phys Biol. 2009 Feb 10;6(1):015004. doi: 10.1088/1478-3975/6/1/015004.
The effect of surface tethering on the folding mechanism of the src-SH3 protein domain was investigated using a coarse-grained Gō-type protein model. The protein was tethered at various locations along the protein chain and the thermodynamics and kinetics of folding were studied using replica exchange and constant temperature Langevin dynamics. Our simulations reveal that tethering in a structured part of the transition state can dramatically alter the folding mechanism, while tethering in an unstructured part leaves the folding mechanism unaltered as compared to bulk folding. Interestingly, there is only modest correlation between the tethering effect on the folding mechanism and its effect on thermodynamic stability and folding rates. We suggest locations on the protein at which tethering could be performed in single-molecule experiments so as to leave the folding mechanism unaltered from the bulk.
使用粗粒度的Gō型蛋白质模型研究了表面束缚对src-SH3蛋白结构域折叠机制的影响。该蛋白质在蛋白质链的不同位置被束缚，并使用副本交换和恒温朗之万动力学研究了折叠的热力学和动力学。我们的模拟结果表明，在过渡态的结构化部分进行束缚会显著改变折叠机制，而在非结构化部分进行束缚时，与整体折叠相比，折叠机制不变。有趣的是，束缚对折叠机制的影响与其对热力学稳定性和折叠速率的影响之间只有适度的相关性。我们提出了在单分子实验中可以进行束缚的蛋白质上的位置，以便使折叠机制与整体情况保持不变。
