Characterizing macromolecular kinetics from molecular dynamics (MD) simulations requires a distance metric that can distinguish slowly-interconverting states. Here we build upon diffusion map theory and define a kinetic distance for irreducible Markov processes that quantifies how slowly molecular conformations interconvert. The kinetic distance can be computed given a model that approximates the eigenvalues and eigenvectors (reaction coordinates) of the MD Markov operator. Here we employ the time-lagged independent component analysis (TICA). The TICA components can be scaled to provide a kinetic map in which the Euclidean distance corresponds to the kinetic distance. As a result, the question of how many TICA dimensions should be kept in a dimensionality reduction approach becomes obsolete, and one parameter less needs to be specified in the kinetic model construction. We demonstrate the approach using TICA and Markov state model (MSM) analyses for illustrative models, protein conformation dynamics in bovine pancreatic trypsin inhibitor and protein-inhibitor association in trypsin and benzamidine.
MSM/RD: Coupling Markov state models of molecular kinetics with reaction-diffusion simulations
分子动力学（MD）模拟可以模拟大分子之间的相互作用，具有高时空分辨率，但在一个高的计算成本。通过将高通量MD与马尔可夫状态模型（MSM）相结合，现在可以获得小到中等生物分子和复合物的长时间尺度行为。为了模拟大尺度下许多分子的相互作用，基于粒子的反应扩散（RD）模拟更合适，但缺乏分子细节。因此，耦合MSM和RD模拟（MSM/RD）将是非常可取的，因为它们可以有效地产生模拟在大的时间和长度尺度，同时仍然保存在原子细节观察到的相互作用的特征。虽然这样的耦合看起来很简单，但基本问题仍然是开放的：MSM状态的定义是合适的？在缔合/解离反应中，哪种合并和分裂RD粒子的方案将保持正确的双分子动力学和热力学？在本文中，我们向MSM/RD迈出了第一步，通过布局耦合的一般理论，并提出了第一个实施的关联/解离的蛋白质与一个小的配体（A + B <-->C）。应用玩具模型和CO扩散到血红素腔肌红蛋白的报告。
Kinetic modeling of molecular beam formation in a cryogenic buffer-gas cell
Vienna Center for Quantum Science and Technology, Atominstitut, TU Wien（维也纳量子科学与技术中心，原子研究所，维也纳工业大学）；LSS, Faculty of Engineering, Friedrich-Alexander-Universität Erlangen-Nürnberg（埃尔朗根-纽伦堡大学工程学院）；Institute of Space Systems, University of Stuttgart（斯图加特大学空间系统研究所）
Responding to objections made by Sorin Coşofreţ concerning kinetic molecular theory: an illustration of how to teach physics students to evaluate pseudoscientific work
