J Phys Chem B. 2019 Feb 14;123(6):1228-1236. doi: 10.1021/acs.jpcb.8b09318. Epub 2019 Feb 5.
Force probe methods are routinely used to study conformational transitions of biomolecules at single-molecule level. In contrast to simple kinetics, some proteins show complex response to mechanical perturbations that is manifested in terms of unusual force-dependent kinetics. Here, we study, via fully atomistic molecular dynamics simulations, constant force-induced unfolding of ubiquitin protein. Our simulations reveal a crossover at an intermediate force (about 400 pN) in the unfolding rate versus force curve. We find by calculation of multidimensional free-energy landscape (FEL) of the protein that the complex unfolding kinetics is intimately related to the force-dependent modifications in the FEL. Pearson correlation coefficient analysis allowed us to identify two appropriate order parameters describing the unfolding transition. The crossover in the rate can be explained in terms of an interplay between entropy and enthalpy with relative importance changing from low force to high force. We rationalize the results by using multidimensional transition-state theory.
力探针方法通常用于在单分子水平上研究生物分子的构象转变。与简单的动力学不同，一些蛋白质对机械扰动表现出复杂的响应，表现在异常的力依赖动力学方面。在这里，我们通过全原子分子动力学模拟研究了泛素蛋白在恒定力下的展开。我们的模拟揭示了在展开速率与力曲线的中间力（约 400 pN）处的交叉。我们通过计算蛋白质的多维自由能景观（FEL）发现，复杂的展开动力学与 FEL 中力依赖性的修饰密切相关。Pearson 相关系数分析使我们能够识别出两个描述展开跃迁的合适的序参量。速率中的交叉可以用熵和焓的相互作用来解释，随着力的增加，相对重要性从低力到高力发生变化。我们使用多维过渡态理论来合理化这些结果。
