Biomolecular Dynamics, Institute of Physics, University of Freiburg, Freiburg 79104, Germany.
J Chem Theory Comput. 2024 Jun 25;20(12):5058-5067. doi: 10.1021/acs.jctc.4c00250. Epub 2024 Jun 12.
Understanding the dynamics of biomolecular complexes, e.g., of protein-ligand (un)binding, requires the comprehension of paths such systems take between metastable states. In MD simulations, paths are usually not observable per se, but they need to be inferred from simulation trajectories. Here, we present a novel approach to cluster trajectories based on a community detection algorithm that necessitates only the definition of a single parameter. The unbinding of the streptavidin-biotin complex is used as a benchmark system and the A adenosine receptor in complex with the inhibitor ZM241385 as an elaborate application. We demonstrate how such clusters of trajectories correspond to pathways and how the approach helps in the identification of reaction coordinates for a considered (un)binding process.
理解生物分子复合物的动力学，例如蛋白质-配体（解）结合，需要理解系统在亚稳态之间所采取的路径。在 MD 模拟中，路径本身通常是不可观察的，但需要从模拟轨迹中推断出来。在这里，我们提出了一种基于社区检测算法的聚类轨迹的新方法，该方法只需要定义一个参数。以链霉亲和素-生物素复合物的解键合作为基准系统，并用腺苷 A 受体与其抑制剂 ZM241385 的复合物作为一个精细的应用实例。我们演示了这样的轨迹簇如何对应于途径，以及该方法如何帮助确定所考虑的（解）键合过程的反应坐标。
