Spiwok Vojtech, Lipovová Petra, Králová Blanka
J Phys Chem B. 2007 Mar 29;111(12):3073-6. doi: 10.1021/jp068587c. Epub 2007 Mar 6.
We propose an approach that combines an extraction of collective motions of a molecular system with a sampling of its free energy surface. A recently introduced method of metadynamics allows exploration of the free energy surface of a molecular system by means of coarse-grained dynamics with flooding of free energy minima. This free energy surface is defined as a function of a set of collective variables (e.g., interatomic distances, angles, torsions, and others). In this study, essential coordinates determined by essential dynamics (principle component analysis) were used as collective variables in metadynamics. First, dynamics of the model system (explicitly solvated alanine dipeptide, Ace-Ala-Nme) was simulated by a classical molecular dynamics simulation. The trajectory (1 ns) was then analyzed by essential dynamics to obtain essential coordinates. The free energy surface as a function of the first and second essential coordinates was then explored by metadynamics. The resulting free energy surface is in agreement with other studies of this system. We propose that a combination of these two methods (metadynamics and essential dynamics) has great potential in studies of conformational changes in peptides and proteins.
我们提出了一种将分子系统的集体运动提取与自由能面采样相结合的方法。最近引入的元动力学方法允许通过粗粒度动力学和自由能最小值的填充来探索分子系统的自由能面。这个自由能面被定义为一组集体变量（例如，原子间距离、角度、扭转等）的函数。在本研究中，由主成分分析确定的主坐标被用作元动力学中的集体变量。首先，通过经典分子动力学模拟对模型系统（明确溶剂化的丙氨酸二肽，Ace-Ala-Nme）的动力学进行模拟。然后通过主成分分析对轨迹（1 ns）进行分析以获得主坐标。接着通过元动力学探索作为第一和第二主坐标函数的自由能面。所得的自由能面与该系统的其他研究结果一致。我们认为这两种方法（元动力学和主成分分析）的结合在肽和蛋白质构象变化的研究中具有巨大潜力。
