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

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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.