Branduardi Davide, Faraldo-Gómez José D
Theoretical Molecular Biophysics Group, Max Planck Institute of Biophysics, Max-von-Laue Strasse 3, DE-60438, Frankfurt-am-Main, Germany.
J Chem Theory Comput. 2013 Sep 10;9(9):4140-4154. doi: 10.1021/ct400469w.
The string method is a molecular-simulation technique that aims to calculate the minimum free-energy path of a chemical reaction or conformational transition, in the space of a pre-defined set of reaction coordinates that is typically highly dimensional. Any descriptor may be used as a reaction coordinate, but arguably the Cartesian coordinates of the atoms involved are the most unprejudiced and intuitive choice. Cartesian coordinates, however, present a non-trivial problem, in that they are not invariant to rigid-body molecular rotations and translations, which ideally ought to be unrestricted in the simulations. To overcome this difficulty, we reformulate the framework of the string method to integrate an on-the-fly structural-alignment algorithm. This approach, referred to as SOMA (String method with Optimal Molecular Alignment), enables the use of Cartesian reaction coordinates in freely tumbling molecular systems. In addition, this scheme permits the dissection of the free-energy change along the most probable path into individual atomic contributions, thus revealing the dominant mechanism of the simulated process. This detailed analysis also provides a physically-meaningful criterion to coarse-grain the representation of the path. To demonstrate the accuracy of the method we analyze the isomerization of the alanine dipeptide in vacuum and the chair-to-inverted-chair transition of -D mannose in explicit water. Notwithstanding the simplicity of these systems, the SOMA approach reveals novel insights into the atomic mechanism of these isomerizations. In both cases, we find that the dynamics and the energetics of these processes are controlled by interactions involving only a handful of atoms in each molecule. Consistent with this result, we show that a coarse-grained SOMA calculation defined in terms of these subsets of atoms yields nearidentical minimum free-energy paths and committor distributions to those obtained via a highly-dimensional string.
弦方法是一种分子模拟技术，旨在计算化学反应或构象转变在一组预先定义的反应坐标空间中的最小自由能路径，该坐标空间通常是高维的。任何描述符都可以用作反应坐标，但可以说所涉及原子的笛卡尔坐标是最无偏见且直观的选择。然而，笛卡尔坐标存在一个重要问题，即它们对于刚体分子的旋转和平移不是不变的，而在模拟中理想情况下这些旋转和平移应该是不受限制的。为了克服这个困难，我们重新构建了弦方法的框架，以集成一种实时结构对齐算法。这种方法，称为SOMA（具有最优分子对齐的弦方法），能够在自由翻滚的分子系统中使用笛卡尔反应坐标。此外，该方案允许将沿着最可能路径的自由能变化分解为各个原子的贡献，从而揭示模拟过程的主导机制。这种详细的分析还提供了一个具有物理意义的标准，用于对路径表示进行粗粒化。为了证明该方法的准确性，我们分析了真空中丙氨酸二肽的异构化以及在明确水环境中β-D-甘露糖的椅式到反椅式转变。尽管这些系统很简单，但SOMA方法揭示了这些异构化原子机制的新见解。在这两种情况下，我们发现这些过程的动力学和能量学仅由每个分子中少数几个原子之间的相互作用控制。与这个结果一致，我们表明根据这些原子子集定义的粗粒化SOMA计算产生的最小自由能路径和反应几率分布与通过高维弦获得的结果几乎相同。
