Statistical analysis of conformational changes of proteins

随着计算机硬件和软件的最新发展，模拟生物分子的功能相关构象变化成为可能。然而，另一方面，仿真数据量迅速增加，在没有统计分析的情况下处理如此大量的数据变得越来越困难。在这项研究中，我们开发了一个对分子动力学模拟数据进行统计分析的框架。所开发的框架被成功地应用于两种情况的构象变化数据：(I)从9微秒的模拟数据中确定了腺苷酸激酶最慢的自由度(涉及P环和铰链区)。(Ii)成功地评估了多药转运蛋白AcrB构象变化途径上的自由能差异。

With the help of recent advances in computer hardware and software, it is becoming possible to simulate functionally relevant conformational changes of biomolecules. On the other hand, however, the amount of simulation data is rapidly increasing and it is becoming difficult to treat such large amount of data without statistical analysis. In this study, we have developed a framework for the statistical analysis of molecular dynamics simulation data. The developed framework was successfully applied to conformational change data of two cases: (i) The most slowest degrees of freedom (involving the P-loop and a hinge region) in Adenylate Kinase was identified from 9 microseconds simulation data. (ii) Free energy differences along the conformational change pathways of multidrug transporter AcrB was successfully evaluated.