Department of Physics, Florida International University, University Park, Miami, Florida 33199, USA.
J Phys Chem B. 2010 Jan 21;114(2):796-803. doi: 10.1021/jp909872a.
We use computer simulations to investigate the influence of salt bridges on the dimerization of the GCN4 leucine zipper. Use of a lattice model allows the dimerization process to be followed for time scales long enough to investigate large-scale structural changes traversing large distances in configuration space. We calculated the rate, efficiency, and stability of dimerization and free-energy landscapes. We varied the strength of the ionic interactions and find that there is an optimal, intermediate salt bridge strength at which the dimerization process proceeds at the maximum rate. Though especially strong salt bridge strength beneficially stabilizes native dimers if they form, it can also stabilize non-native configurations that can hinder the dimerization process. We give examples of stable, non-native structures that might arise. These structures may be relevant to interesting recent experiments that have provided evidence of unusual forms of the leucine zipper GCN4-p1 called the LZ(GCN4) x-forms, which dominate the population in certain biochemical conditions.
我们使用计算机模拟来研究盐桥对 GCN4 亮氨酸拉链二聚体的影响。使用晶格模型可以使二聚化过程能够在足够长的时间尺度上进行跟踪，以研究跨越构象空间中较大距离的大规模结构变化。我们计算了二聚化和自由能景观的速率、效率和稳定性。我们改变了离子相互作用的强度，发现存在一个最佳的中间盐桥强度，在该强度下，二聚化过程以最大速率进行。尽管特别强的盐桥强度如果形成的话可以有益地稳定天然二聚体，但它也可以稳定可能阻碍二聚化过程的非天然构象。我们给出了可能出现的稳定非天然结构的例子。这些结构可能与最近的一些有趣实验有关，这些实验提供了亮氨酸拉链 GCN4-p1 的异常形式（称为 LZ(GCN4) x 形式）的证据，在某些生化条件下，这些形式占据主导地位。
