Computational Biophysics Research Team, RIKEN Center for Computational Science, Kobe, Hyogo, 650-0047, Japan.
Theoretical Molecular Science Laboratory, RIKEN Cluster for Pioneering Research, Wako, Saitama, 351-0198, Japan.
Nat Commun. 2024 Apr 20;15(1):3370. doi: 10.1038/s41467-024-47654-1.
Residue-level coarse-grained (CG) molecular dynamics (MD) simulation is widely used to investigate slow biological processes that involve multiple proteins, nucleic acids, and their complexes. Biomolecules in a large simulation system are distributed non-uniformly, limiting computational efficiency with conventional methods. Here, we develop a hierarchical domain decomposition scheme with dynamic load balancing for heterogeneous biomolecular systems to keep computational efficiency even after drastic changes in particle distribution. These schemes are applied to the dynamics of intrinsically disordered protein (IDP) droplets. During the fusion of two droplets, we find that the changes in droplet shape correlate with the mixing of IDP chains. Additionally, we simulate large systems with multiple IDP droplets, achieving simulation sizes comparable to those observed in microscopy. In our MD simulations, we directly observe Ostwald ripening, a phenomenon where small droplets dissolve and their molecules redeposit into larger droplets. These methods have been implemented in CGDYN of the GENESIS software, offering a tool for investigating mesoscopic biological processes using the residue-level CG models.
残基粗粒化（CG）分子动力学（MD）模拟广泛用于研究涉及多种蛋白质、核酸及其复合物的缓慢生物过程。在一个大的模拟系统中，生物分子的分布不均匀，这限制了传统方法的计算效率。在这里，我们开发了一种具有动态负载平衡的层次域分解方案，用于异质生物分子系统，以保持计算效率，即使在粒子分布发生剧烈变化时也是如此。这些方案应用于固有无序蛋白（IDP）液滴的动力学研究。在两个液滴融合的过程中，我们发现液滴形状的变化与 IDP 链的混合有关。此外，我们还模拟了具有多个 IDP 液滴的大型系统，实现了与显微镜观察到的大小相当的模拟尺寸。在我们的 MD 模拟中，我们直接观察到奥斯特瓦尔德熟化现象，即小液滴溶解，其分子重新沉积到较大的液滴中。这些方法已经在 GENESIS 软件的 CGDYN 中实现，为使用残基 CG 模型研究介观生物过程提供了一种工具。
