Molecular dynamics simulations of reversible hydrogen bond network dynamics under external force

机械力的应用可以打破超分子组合中的粘附键或展开生物分子。解结合率的力依赖性在单分子水平上提供了动力学的重要信息。在该项目中，将对具有可逆解键和再键的系统进行外力影响下的分子动力学模拟。与只显示不可逆解结合的系统相比，这里有机会同时观察解结合和再结合，从而可以对动力学进行详细的研究。特别是，它应该能够观察到简单的两态动力学的偏差，并分析中间体的影响。此外，可以详细研究观察到的力作为分子扩展的函数的典型非平衡特征，如滞后。大多数在实验研究中表现为可逆的系统在分子动力学模拟的快速时间尺度上表现为不可逆行为。因此，我们将使用一类具有链烷结构的纠缠分子（杯芳烃链烷）作为模型系统，因为这些系统中的环结构可以防止完全解离，并且可以观察到结构的可逆打开。该项目最重要的目标是了解相关能量景观参数的力依赖性，如解绑定和再绑定的动力学速率。由于通过不同协议施加的外力以不同的方式使系统脱离热平衡，因此研究产生的速率是否可以直接相互比较是很重要的。为此，将计算和分析在恒定外力影响下的所谓双态轨迹。所得的速率将与计算平均力势作为分子沿拉力方向延伸的函数所得的速率进行比较。改变杯芳烃二聚体的环长会改变键断裂和键形成的动力学行为。对于短环，可以观察到简单的两态动力学，而对于长环，不仅可以发现开态和闭态，还可以发现中间态。因此，对模型系统稍加修改，就可以研究简单动力学的偏差，并研究可逆动力学中中间体的影响。这些研究可以验证现有的粘附键力依赖特性的理论模型，并有助于加深对复杂系统动力学行为的理解。

The application of a mechanical force allows to break adhesion bonds in supramolecular assemblies or to unfold biomolecules. The force-dependence of the unbinding rate yields important information about the kinetics on a single molecule level.In the project molecular dynamics simulations under the influence of an external force will be performed on systems showing reversible unbinding and rebinding. In contrast to the much studied systems showing only irreversible unbinding, here the opportunity to observe both, unbinding and rebinding, allows for a detailed study of the kinetics. In particular, it should be possible to observe deviations from a simple two-state kinetics and to analyze the impact of intermediates. Furthermore, plotting the observerd force as a function of the molecular extension typical non-equilibrium features like hysteresis can be studied in detail. Most of the systems that appear reversible in experimental studies show irreversible behavior on the fast time scale of molecular dynamics simulations. Therefore, we will use a class of entangled molecules with a catenane structure (calixarene catenanes) as model systems because complete dissociation in these systems is prevented by the loop structure and reversible opening of the structure can be observed. The most important goal of the project is to understand the force-dependence of relevant energy landscape parameters like the kinetic rates for unbinding and rebinding. Since the application of the external force via different protocols drives the system out of thermal equilibrium in different ways, it is important to investigate whether the resulting rates can be directly compared to each other. For this purpose, so-called two-state trajectories under the influence of a constant external force will be computed and analyzed. The resulting rates will be compared to those obtained from calculations of the potential of mean force as a function of the molecular extension along the pulling direction. Changing the loop length of the calixarene dimers investigated gives rise to a change in the kinetic behavior of bond rupture and bond formation. For short loops a simple two-state kinetics is observed while for longer loops one finds not only an open and a closed state but also an intermediate. Thus, a slight modification of the model system allows to study deviations from a simple kinetics and to investigate the impact of an intermediate in the reversible dynamics. The investigations allow to validate existing theoretical models for the force-dependent properties of adhesion bonds and may help to deepen the understanding of the kinetic behavior of complex systems.