Projected and hidden Markov models for calculating kinetics and metastable states of complex molecules
Projected and hidden Markov models for calculating kinetics and metastable states of complex molecules
复制标题
DOI：
10.1063/1.4828816
复制
发表时间：
2013-11-14
影响因子：
4.4
通讯作者：
Plattner, Nuria
中科院分区：
文献类型：
--
作者：
Noe, Frank;Wu, Hao;Plattner, Nuria
马尔可夫状态模型(MSM)已经成功地从大量的分子动力学模拟数据中计算了复杂分子的亚稳态、慢弛豫时间尺度和相关的结构变化，以及静态或动态的实验观察值。然而，MSM通过假设状态空间的簇离散化上的马尔可夫链来近似真实的动态。这种近似很难适用于高维生物分子系统，因此，MSM的质量和重复性受到了限制。在这里，我们放弃了离散集群上的动力学是马尔可夫的假设。相反，我们只假设全相空间分子动力学是马尔可夫的，并且这种全动力学在离散状态上的投影被观察到，从而产生了投影马尔可夫模型(PMM)的概念。关于PMM的稳健估计方法尚不存在，但我们通过隐马尔可夫模型(HMM)得到了一个实际可行的近似。它展示了如何从HMM/PMM计算出通常由MSM计算的各种感兴趣的分子观察量。新框架适用于模拟数据和单分子实验数据。我们通过在教育模型系统中的应用，1毫秒的牛胰蛋白酶抑制蛋白的Anton MD模拟，以及RNA发夹的光镊力探针轨迹的应用，展示了它的多功能性。(C)2013 AIP出版有限责任公司。
Markov state models (MSMs) have been successful in computing metastable states, slow relaxation timescales and associated structural changes, and stationary or kinetic experimental observables of complex molecules from large amounts of molecular dynamics simulation data. However, MSMs approximate the true dynamics by assuming a Markov chain on a clusters discretization of the state space. This approximation is difficult to make for high-dimensional biomolecular systems, and the quality and reproducibility of MSMs has, therefore, been limited. Here, we discard the assumption that dynamics are Markovian on the discrete clusters. Instead, we only assume that the full phase-space molecular dynamics is Markovian, and a projection of this full dynamics is observed on the discrete states, leading to the concept of Projected Markov Models (PMMs). Robust estimation methods for PMMs are not yet available, but we derive a practically feasible approximation via Hidden Markov Models (HMMs). It is shown how various molecular observables of interest that are often computed from MSMs can be computed from HMMs/PMMs. The new framework is applicable to both, simulation and single-molecule experimental data. We demonstrate its versatility by applications to educative model systems, a 1 ms Anton MD simulation of the bovine pancreatic trypsin inhibitor protein, and an optical tweezer force probe trajectory of an RNA hairpin. (C) 2013 AIP Publishing LLC.