论文标题
分子潜在空间模拟器
Molecular Latent Space Simulators
论文作者
论文摘要
小集成时间步骤将分子动力学(MD)模拟限制为毫秒时间尺度。 Markov状态模型(MSMS)和无方程方法通过执行状态空间的配置或动态粗粒度从MD模拟数据中学习低维动力学模型。学到的动力学模型能够在时间尺度上有效地生成动力轨迹的有效产生,而不是通过MD访问,但是配置空间的离散化和/或缺乏一种重建分子构型的方法阻止了连续全元原子轨迹的产生。我们建议潜在的空间模拟器(LSS)通过训练三个深度学习网络来学习连续的全原子模拟轨迹的动力学模型,以了解分子系统的慢速集体变量,(ii)在此缓慢的潜在空间中传播系统动力学,并且(iii)(iii)通常重建分子构型。我们证明了在TRP笼小蛋白应用中的应用中,以产生新的超长合成折叠轨迹,该轨迹准确地以比MD低的六个数量级成本准确地重现了全原子分子结构,热力学和动力学。轨迹产生的成本急剧降低,可以大大改善采样,并大大降低了估计的热力学平均值和动力学速率的统计不确定性。
Small integration time steps limit molecular dynamics (MD) simulations to millisecond time scales. Markov state models (MSMs) and equation-free approaches learn low-dimensional kinetic models from MD simulation data by performing configurational or dynamical coarse-graining of the state space. The learned kinetic models enable the efficient generation of dynamical trajectories over vastly longer time scales than are accessible by MD, but the discretization of configurational space and/or absence of a means to reconstruct molecular configurations precludes the generation of continuous all-atom molecular trajectories. We propose latent space simulators (LSS) to learn kinetic models for continuous all-atom simulation trajectories by training three deep learning networks to (i) learn the slow collective variables of the molecular system, (ii) propagate the system dynamics within this slow latent space, and (iii) generatively reconstruct molecular configurations. We demonstrate the approach in an application to Trp-cage miniprotein to produce novel ultra-long synthetic folding trajectories that accurately reproduce all-atom molecular structure, thermodynamics, and kinetics at six orders of magnitude lower cost than MD. The dramatically lower cost of trajectory generation enables greatly improved sampling and greatly reduced statistical uncertainties in estimated thermodynamic averages and kinetic rates.