Sidler Dominik, Lehner Marc, Frasch Simon, Cristófol-Clough Michael, Riniker Sereina
Laboratory of Physical Chemistry, ETH Zürich, Zurich, 8093, Switzerland.
F1000Res. 2018 Nov 5;7:1745. doi: 10.12688/f1000research.16715.3. eCollection 2018.
Molecular dynamics (MD) simulations have become an important tool to provide insight into molecular processes involving biomolecules such as proteins, DNA, carbohydrates and membranes. As these processes cover a wide range of time scales, multiple time-step integration methods are often employed to increase the speed of MD simulations. For example, in the twin-range (TR) scheme, the nonbonded forces within the long-range cutoff are split into a short-range contribution updated every time step (inner time step) and a less frequently updated mid-range contribution (outer time step). The presence of different time steps can, however, cause numerical artefacts. The effects of multiple time-step algorithms at interfaces between polar and apolar media are investigated with MD simulations. Such interfaces occur with biological membranes or proteins in solution. In this work, it is shown that the TR splitting of the nonbonded forces leads to artificial density increases at interfaces for weak coupling and Nosé-Hoover (chain) thermostats. It is further shown that integration with an impulse-wise reversible reference system propagation algorithm (RESPA) only shifts the occurrence of density artefacts towards larger outer time steps. Using a single-range (SR) treatment of the nonbonded interactions or a stochastic dynamics thermostat, on the other hand, resolves the density issue for pairlist-update periods of up to 40 fs. TR schemes are not advisable to use in combination with weak coupling or Nosé-Hoover (chain) thermostats due to the occurrence of significant numerical artifacts at interfaces.
分子动力学（MD）模拟已成为一种重要工具，可用于深入了解涉及蛋白质、DNA、碳水化合物和膜等生物分子的分子过程。由于这些过程涵盖了广泛的时间尺度，因此常采用多时间步积分方法来提高MD模拟的速度。例如，在双范围（TR）方案中，长程截止范围内的非键合力被分为每次时间步更新的短程贡献（内时间步）和更新频率较低的中程贡献（外时间步）。然而，不同时间步的存在可能会导致数值伪影。通过MD模拟研究了多时间步算法在极性和非极性介质界面处的影响。这种界面存在于生物膜或溶液中的蛋白质中。在这项工作中，结果表明，对于弱耦合和Nosé-Hoover（链）恒温器，非键合力的TR分裂会导致界面处出现人为的密度增加。进一步表明，使用脉冲式可逆参考系统传播算法（RESPA）进行积分只会将密度伪影的出现转移到更大的外时间步。另一方面,对于长达40 fs的对列表更新周期，使用非键相互作用的单范围（SR）处理或随机动力学恒温器可解决密度问题由于在界面处会出现明显的数值伪影，因此不建议将TR方案与弱耦合或Nosé-Hoover（链）恒温器结合使用。
