Accelerating Membrane Simulations with Hydrogen Mass Repartitioning

The time step of atomistic molecular dynamics (MD) simulations is determined by the fastest motions in the system and is typically limited to 2 fs. An increasingly popular approach is to increase the mass of the hydrogen atoms to ∼3 amu and decrease the mass of the parent atom by an equivalent amount. This approach, known as hydrogen-mass repartitioning (HMR), permits time steps up to 4 fs with reasonable simulation stability. While HMR has been applied in many published studies to date, it has not been extensively tested for membrane-containing systems. Here, we compare the results of simulations of a variety of membranes and membrane–protein systems run using a 2 fs time step and a 4 fs time step with HMR. For pure membrane systems, we find almost no difference in structural properties, such as area-per-lipid, electron density profiles, and order parameters, although there are differences in kinetic properties such as the diffusion constant. Conductance through a porin in an applied field, partitioning of a small peptide, hydrogen-bond dynamics, and membrane mixing show very little dependence on HMR and the time step. We also tested a 9 Å cutoff as compared to the standard CHARMM cutoff of 12 Å, finding significant deviations in many properties tested. We conclude that HMR is a valid approach for membrane systems, but a 9 Å cutoff is not.全原子分子动力学（MD）模拟的时间步长由体系内最快的运动过程决定，通常被限定为2飞秒（fs）。当前愈发流行的一种优化策略为：将氢原子的质量提升至约3原子质量单位（amu），同时将其母原子的质量等量降低。这种被称为氢质量再分配（HMR）的技术，可将模拟时间步长提升至4飞秒，且仍能维持合理的模拟稳定性。尽管氢质量再分配技术迄今已在大量已发表的研究中得到应用，但针对含膜体系的系统性测试仍较为匮乏。本研究对比了采用2飞秒时间步长，以及搭载氢质量再分配技术的4飞秒时间步长，对多种膜体系与膜蛋白体系开展模拟的结果。对于纯膜体系，尽管在扩散系数等动力学性质上存在一定差异，但在脂单分子层面积、电子密度分布以及有序参数等结构性质上几乎无显著区别。外加电场下孔蛋白的跨膜电导、小肽的膜分配行为、氢键动力学以及膜混合过程，均几乎不受氢质量再分配技术与时间步长的影响。我们还对比了9埃（Å）截断半径与标准CHARMM 12埃（Å）截断半径的模拟效果，发现多项测试性质均出现显著偏差。综上，氢质量再分配技术适用于膜体系模拟，但9埃截断方案并不可取。