Molecular dynamics (MD) simulation software allows probing the equilibrium structural dynamics of a molecule of interest, revealing how a molecule navigates its structure space one structure at a time. To obtain a broader view of dynamics, typically one needs to launch many such simulations, obtaining many trajectories. A summarization of the equilibrium dynamics requires integrating the information in the various trajectories, and Markov State Models (MSM) are increasingly being used for this task. At its core, the task involves organizing the structures accessed in simulation into structural states, and then constructing a transition probability matrix revealing the transitions between states. While now considered a mature technology and widely used to summarize equilibrium dynamics, the underlying computational process in the construction of an MSM ignores energetics even though the transition of a molecule between two nearby structures in an MD trajectory is governed by the corresponding energies. In this paper, we connect theory with simulation and analysis of equilibrium dynamics. A molecule navigates the energy landscape underlying the structure space. The structural states that are identified via off-the-shelf clustering algorithms need to be connected to thermodynamically-stable and semi-stable (macro)states among which transitions can then be quantified. Leveraging recent developments in the analysis of energy landscapes that identify basins in the landscape, we evaluate the hypothesis that basins, directly tied to stable and semi-stable states, lead to better models of dynamics. Our analysis indicates that basins lead to MSMs of better quality and thus can be useful to further advance this widely-used technology for summarization of molecular equilibrium dynamics.

中文翻译：

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通过景观分析和马尔可夫状态模型从分子能量景观到平衡动力学

分子动力学 (MD) 模拟软件允许探测感兴趣分子的平衡结构动力学，揭示分子如何一次在其结构空间中导航一个结构。为了获得更广泛的动力学视图，通常需要启动许多这样的模拟，获得许多轨迹。平衡动力学的总结需要整合各种轨迹中的信息，马尔可夫状态模型 (MSM) 越来越多地用于这项任务。该任务的核心是将模拟中访问的结构组织成结构状态，然后构建一个转换概率矩阵，揭示状态之间的转换。虽然现在被认为是一种成熟的技术并广泛用于总结平衡动力学，即使分子在 MD 轨迹中两个附近结构之间的跃迁受相应能量的控制，MSM 构建中的基本计算过程也忽略了能量学。在本文中，我们将理论与平衡动力学的模拟和分析联系起来。分子在结构空间下的能量景观中导航。通过现成的聚类算法识别的结构状态需要连接到热力学稳定和半稳定（宏观）状态，然后可以量化其中的转变。利用识别景观中盆地的能源景观分析的最新进展，我们评估了与稳定和半稳定状态直接相关的盆地可以产生更好的动力学模型的假设。