Sengul Mert Y, MacKerell Alexander D
Department of Pharmaceutical Sciences, School of Pharmacy, University of Maryland, Baltimore, Maryland, 21201.
J Comput Biophys Chem. 2022 Jun;21(4):461-471. doi: 10.1142/s2737416521420060. Epub 2022 Jan 26.
Molecular dynamics (MD) simulations play a crucial role in modeling biomolecular systems in which the electrostatic interactions are critical in dictating the structural and dynamical properties. Thus, the treatment of the electrostatic interactions defined in the underlying force field (FF) strongly affects the simulation accuracy. Most FFs use fixed partial atomic charges to include electrostatic interactions, and therefore lack the electronic polarization response, representing an intrinsic limitation. To address this limitation, polarizable FFs have been developed that treat atomic polarizabilities explicitly. Here we present the application of the all-atom polarizable (Drude) and non-polarizable (CHARMM) nucleic acid FFs in RNA hairpin systems to investigate the impact of polarization on structural properties, dipole moment distributions, and cation interactions. Results show that the presence of polarizability in the FF significantly improves the stabilization of RNA hairpin structure. As expected, the distributions of dipole moments show more fluctuations when simulated using the polarizable FF, with the variation in dipoles contributing to the stabilization of the structures of the loop regions of the RNAs. Contact map analyses between the bases and cations show that the variation of the ion distribution around the entire hairpin is larger for the polarizable FF and the cations occupy the outer hydration shell to a greater extent. The presented results indicate the importance of the explicit treatment of electronic polarizability in molecular simulations of RNA, including in non-canonical regions.
分子动力学（MD）模拟在生物分子系统建模中起着至关重要的作用，其中静电相互作用对于决定结构和动力学性质至关重要。因此，基础力场（FF）中定义的静电相互作用的处理方式会强烈影响模拟精度。大多数力场使用固定的部分原子电荷来包含静电相互作用，因此缺乏电子极化响应，这是一个内在的局限性。为了解决这个局限性，已经开发了可极化力场，其明确处理原子极化率。在这里，我们展示了全原子可极化（德鲁德）和不可极化（CHARMM）核酸力场在RNA发夹系统中的应用，以研究极化对结构性质、偶极矩分布和阳离子相互作用的影响。结果表明，力场中极化率的存在显著提高了RNA发夹结构的稳定性。正如预期的那样，使用可极化力场进行模拟时，偶极矩的分布显示出更多的波动，偶极子的变化有助于RNA环区域结构的稳定。碱基与阳离子之间的接触图分析表明，对于可极化力场，整个发夹周围离子分布的变化更大，并且阳离子在更大程度上占据外部水合壳层。所呈现的结果表明，在RNA的分子模拟中，包括在非规范区域中，明确处理电子极化率非常重要。
