Zhu Wentao, Zhang Jian, Wang Jun, Li Wenfei, Wang Wei
School of Physics, National Laboratory of Solid State Microstructure, and Collaborative Innovation Center of Advanced Microstructures, Nanjing University, Nanjing 210093, China.
Phys Rev E. 2021 Mar;103(3-1):032404. doi: 10.1103/PhysRevE.103.032404.
The sampling of conformations in the molecular simulations for systems with complicated free energy landscapes is always difficult. Here, we report a method for enhanced sampling based on the coarse-graining of conformational space. In this method, the locally converged region of the conformational space is coarse-grained with its population characterized by the related average residence time and visiting number, and at the same time, the direct simulations inside it are eliminated. The detailed balance is satisfied by updating the visiting number and generating outgoing trajectories of this region. This kind of coarse-graining operation can be further carried out by merging all the neighboring regions which are already converged together. The global equilibrium is achieved when the local equilibrated regions cover all the interested areas of the landscape. We tested the method by applying it to two model potentials and one protein system with multiple-basin energy landscapes. The sampling efficiency is found to be enhanced by more than three orders of magnitude compared to conventional molecular simulations, and are comparable with other widely used enhanced sampling methods. In addition, the kinetic information can also be well captured. All these results demonstrate that our method can help to solve the sampling problems efficiently and precisely without applying high temperatures or biasing potentials.
对于具有复杂自由能景观的系统，在分子模拟中对构象进行采样一直很困难。在此，我们报告一种基于构象空间粗粒化的增强采样方法。在该方法中，构象空间的局部收敛区域被粗粒化，其总体由相关的平均停留时间和访问次数表征，同时消除其内部的直接模拟。通过更新访问次数并生成该区域的出射轨迹来满足细致平衡。这种粗粒化操作可以通过合并所有已经收敛在一起的相邻区域进一步进行。当局部平衡区域覆盖景观的所有感兴趣区域时，实现全局平衡。我们将该方法应用于两个模型势和一个具有多阱能量景观的蛋白质系统来测试它。发现与传统分子模拟相比，采样效率提高了三个多数量级，并且与其他广泛使用的增强采样方法相当。此外，动力学信息也能被很好地捕捉。所有这些结果表明，我们的方法无需应用高温或偏置势就能有效且精确地解决采样问题。
