Conformational dynamics play a crucial role in determining the behavior of the biomolecules. Polarizable force fields, such as AMOEBA, can accurately capture electrostatic interactions underlying the conformational space. However, applying a polarizable force field in molecular dynamics (MD) simulations can be computationally expensive, especially in studying long-time-scale dynamics. To overcome this challenge, we incorporated the AMOEBA potential with Milestoning, an enhanced sampling method in this work. This integration allows us to efficiently sample the rare and important conformational states of a biomolecule by using many short and independent molecular dynamics trajectories with the AMOEBA force field. We applied this method to investigate the conformational dynamics of alanine dipeptide, DNA, and RNA A-B form conversion. Well-converged thermodynamic and kinetic properties were obtained, including the free energy difference, mean first passage time, and critical transitions between states. Our results demonstrate the power of integrating polarizable force fields with enhanced sampling methods in quantifying the thermodynamic and kinetic properties of biomolecules at the atomic level.

中文翻译：

---

利用极化力场 AMOEBA 和增强采样方法里程碑探索生物分子构象动力学


构象动力学在决定生物分子的行为中起着至关重要的作用。可极化力场，例如 AMOEBA，可以准确捕获构象空间下的静电相互作用。然而，在分子动力学 (MD) 模拟中应用极化力场的计算成本可能很高，尤其是在研究长时尺度动力学时。为了克服这一挑战，我们将 AMOEBA 潜力与 Milestoneing（本工作中的一种增强采样方法）结合起来。这种集成使我们能够通过使用许多短且独立的分子动力学轨迹与 AMOEBA 力场来有效地对生物分子的罕见且重要的构象状态进行采样。我们应用这种方法来研究丙氨酸二肽、DNA 和 RNA A-B 形式转换的构象动力学。获得了良好收敛的热力学和动力学性质，包括自由能差、平均首次通过时间和状态之间的临界转变。我们的结果证明了将极化力场与增强的采样方法相结合，可以在原子水平上量化生物分子的热力学和动力学特性。