Institut für Physikalische Chemie, Universität Mainz, Duesbergweg 10-14, 55128 Mainz, Germany.
J Chem Phys. 2017 Mar 28;146(12):124901. doi: 10.1063/1.4978678.
We present a detailed study of the parameter dependence of force probe molecular dynamics (FPMD) simulations. Using a well studied calix[4]arene catenane dimer as a model system, we systematically vary the pulling velocity and the stiffness of the applied external potential. This allows us to investigate how the results of pulling simulations operating in the constant velocity mode (force-ramp mode) depend on the details of the simulation setup. The system studied has the further advantage of showing reversible rebinding meaning that we can monitor the opening and the rebinding transition. Many models designed to extract kinetic information from rupture force distributions work in the limit of soft springs and all quantities are found to depend solely on the so-called loading rate, the product of spring stiffness and pulling velocity. This approximation is known to break down when stiff springs are used, a situation often encountered in molecular simulations. We find that while some quantities only depend on the loading rate, others show an explicit dependence on the spring constant used in the FPMD simulation. In particular, the force versus extension curves show an almost stiffness independent rupture force but the force jump after the rupture transition does depend roughly linearly on the value of the stiffness. The kinetic rates determined from the rupture force distributions show a dependence on the stiffness that can be understood in terms of the corresponding dependence of the characteristic forces alone. These dependencies can be understood qualitatively in terms of a harmonic model for the molecular free energy landscape. It appears that the pulling velocities employed are so large that the crossover from activated dynamics to diffusive dynamics takes place on the time scale of our simulations. We determine the effective distance of the free energy minima of the closed and the open configurations of the system from the barrier via an analysis of the hydrogen-bond network with results in accord with earlier simulations. We find that the system is quite brittle in the force regime monitored in the sense that the barrier is located near to the closed state.
我们对力探针分子动力学（FPMD）模拟的参数依赖性进行了详细研究。使用一个经过充分研究的杯[4]芳烃索烃二聚体作为模型系统，我们系统地改变了拉伸速度和施加的外部势的刚度。这使我们能够研究在恒速模式（力斜坡模式）下进行的拉伸模拟的结果如何取决于模拟设置的细节。所研究的系统具有进一步的优势，即显示出可逆的结合，这意味着我们可以监测打开和重新结合的转变。许多旨在从破裂力分布中提取动力学信息的模型都在软弹簧的极限下工作，并且所有量都仅取决于所谓的加载率，即弹簧刚度和拉伸速度的乘积。当使用硬弹簧时，这种近似会失效，这种情况在分子模拟中经常遇到。我们发现，虽然有些量仅取决于加载率，但其他量则明显取决于 FPMD 模拟中使用的弹簧常数。特别是，力与延伸曲线显示出几乎与刚度无关的破裂力，但破裂转变后的力跃变大致线性依赖于刚度的值。从破裂力分布中确定的动力学速率与刚度有关，这可以根据特征力的相应依赖性来理解。这些依赖性可以根据分子自由能景观的谐波模型进行定性理解。似乎所采用的拉伸速度非常大，以至于从激活动力学到扩散动力学的转变发生在我们的模拟时间尺度上。我们通过分析氢键网络来确定系统的闭合和打开构象的自由能最小值的有效距离与势垒的关系，结果与早期的模拟结果一致。我们发现，系统在监测的力范围内相当脆弱，即势垒位于靠近闭合状态的位置。
