Department of Physics, Florida International University, University Park, Miami, Florida 33199, USA.
J Chem Phys. 2012 Sep 14;137(10):105103. doi: 10.1063/1.4752247.
The folding and dimerization of proteins is greatly facilitated by the presence of a trigger site, a segment of amino acids that has a higher propensity for forming α-helix structure as compared to the rest of the chain. In addition to the helical propensity of each chain, dimerization can also be facilitated by interhelical interactions such as saltbridges, and interfacial contacts of different strengths. In this work, we are interested in understanding the interplay of these interactions in a model peptide system. We investigate how these different interactions influence the kinetics of dimer formation and the stability of the fully formed dimer. We use lattice model computer simulations to investigate how the effectiveness of the trigger segment and its saltbridges depends on the location along the protein primary sequence. For different positions of the trigger segment, heat capacity and free energy of unfolded and folded configurations are calculated to study the thermodynamics of folding and dimerization. The kinetics of the process is investigated by calculating characteristic folding times. The thermodynamic and kinetic data from the simulations combine to show that the dimerization process of the model system is faster when the segment with high helical propensity is located near either end of the peptide, as compared to the middle of the chain. The dependence of the stability of the dimer on the trigger segment's position is also studied. The stability can play a role in the ability of the dimer to perform a biological function that involves partial unzipping. The results on folding and dimer stability provide important insights for designing proteins that involve trigger sites.
蛋白质的折叠和二聚化过程极大地受到触发位点的促进，触发位点是一段氨基酸，与链上的其他部分相比，它更容易形成α-螺旋结构。除了每条链的螺旋倾向外，二聚化还可以通过盐桥等螺旋间相互作用以及不同强度的界面接触来促进。在这项工作中，我们有兴趣了解模型肽系统中这些相互作用的相互作用。我们研究了这些不同的相互作用如何影响二聚体形成的动力学和完全形成的二聚体的稳定性。我们使用格子模型计算机模拟来研究触发片段及其盐桥的有效性如何取决于蛋白质一级序列的位置。对于触发片段的不同位置，计算未折叠和折叠构型的热容和自由能，以研究折叠和二聚化的热力学。通过计算特征折叠时间来研究该过程的动力学。模拟的热力学和动力学数据结合起来表明，与位于链中间相比，当高螺旋倾向的片段位于肽的任一端时，模型系统的二聚化过程更快。还研究了二聚体稳定性对触发片段位置的依赖性。稳定性可以在涉及部分解拉链的二聚体执行生物功能的能力中发挥作用。折叠和二聚体稳定性的结果为涉及触发位点的蛋白质设计提供了重要的见解。
