Pinamonti Giovanni, Paul Fabian, Noé Frank, Rodriguez Alex, Bussi Giovanni
Department for Mathematics and Computer Science, Freie Universität, Berlin, Germany.
Department of Biochemistry and Molecular Biology, Gordon Center for Integrative Science, The University of Chicago, Chicago, Illinois 60637, USA.
J Chem Phys. 2019 Apr 21;150(15):154123. doi: 10.1063/1.5083227.
The process of RNA base fraying (i.e., the transient opening of the termini of a helix) is involved in many aspects of RNA dynamics. We here use molecular dynamics simulations and Markov state models to characterize the kinetics of RNA fraying and its sequence and direction dependence. In particular, we first introduce a method for determining biomolecular dynamics employing core-set Markov state models constructed using an advanced clustering technique. The method is validated on previously reported simulations. We then use the method to analyze extensive trajectories for four different RNA model duplexes. Results obtained using D. E. Shaw research and AMBER force fields are compared and discussed in detail and show a non-trivial interplay between the stability of intermediate states and the overall fraying kinetics.
RNA碱基解链过程（即螺旋末端的瞬时打开）涉及RNA动力学的许多方面。我们在此使用分子动力学模拟和马尔可夫状态模型来表征RNA解链的动力学及其序列和方向依赖性。具体而言，我们首先介绍一种使用先进聚类技术构建的核心集马尔可夫状态模型来确定生物分子动力学的方法。该方法在先前报道的模拟中得到了验证。然后，我们使用该方法分析四种不同RNA模型双链体的大量轨迹。详细比较和讨论了使用D. E. Shaw研究公司和AMBER力场获得的结果，结果表明中间状态的稳定性与整体解链动力学之间存在复杂的相互作用。
