School of Information Science & Engineering, Lanzhou University, Lanzhou, Gansu, China.
J Comput Chem. 2021 Apr 30;42(11):771-786. doi: 10.1002/jcc.26497. Epub 2021 Feb 15.
Molecular dynamics (MD) simulations that rely on force field methods has been widely used to explore the structure and function of RNAs. However, the current commonly used force fields are limited by the electrostatic description offered by atomic charge, dipole and at most quadrupole moments, failing to capture the anisotropic picture of electronic features. Actually, the distribution of electrons around atomic nuclei is not spherically symmetric but is geometry dependent. A multipolar electrostatic model based on high rank multipole moments is described in this work, which allows us to combine polarizability and anisotropy of electron density. RNA secondary structure was taken as a research system, and its substructures including stem, loops (hairpin loop, bulge loop, internal loop, and multi-branch loop), and pseudoknots (H-type and K-type) were investigated, respectively, as well as the hairpin. First, the atom-atom electrostatic properties derived from one chain of a duplex RNA 2MVY in our previous work (Ref. 58) were measured by the pilot RNA systems of hairpin, hairpin loop, stem, and H-type pseudoknot, respectively. The prediction results were not satisfactory. Consequently, to obtain a general set of electrostatic parameters for RNA force fields, the convergence behavior of the atom-atom electrostatic interactions in the pilot RNA systems was explored using high rank atomic multipole moments. The pilot RNA systems were cut into four types of different-sized molecular fragments, and the single nucleotide fragment and nucleotide-paired fragment proved to be the most reasonable systems for base-unpairing regions and base-pairing regions to investigate the convergence behavior of all types of atom-atom electrostatic interactions, respectively. Transferability of the electrostatic properties drawn from the pilot RNA systems to the corresponding test systems was also investigated. Furthermore, the convergence behavior of atomic electrostatic interactions in other substructures including bulge loop, internal loop, multi-branch loop, and K-type pseudoknot was expected to be modeled via the hairpin.
基于力场方法的分子动力学 (MD) 模拟已广泛用于探索 RNA 的结构和功能。然而，当前常用的力场受到原子电荷、偶极子和最多四极矩提供的静电描述的限制，无法捕捉电子特征的各向异性图像。实际上，原子核周围的电子分布不是球对称的，而是依赖于几何形状。本文描述了一种基于高阶多极矩的多极静电模型，它允许我们结合极化率和电子密度的各向异性。以 RNA 二级结构为研究体系，分别研究其亚结构，包括茎、环（发夹环、凸起环、内部环和多分支环）和假结（H 型和 K 型），以及发夹。首先，通过发夹、发夹环、茎和 H 型假结的先导 RNA 系统，分别测量了我们之前工作 (Ref. 58) 中双链 RNA 2MVY 中一条链的原子-原子静电特性。预测结果并不令人满意。因此，为了获得 RNA 力场的一般静电参数集，使用高阶原子多极矩探索了先导 RNA 系统中原子-原子静电相互作用的收敛行为。先导 RNA 系统被切割成四种不同大小的分子片段，单核苷酸片段和核苷酸配对片段被证明是研究碱基非配对区域和碱基配对区域的最合理系统，分别用于研究所有类型原子-原子静电相互作用的收敛行为。还研究了从先导 RNA 系统中得出的静电特性在相应测试系统中的可转移性。此外，预计通过发夹可以模拟其他亚结构（凸起环、内部环、多分支环和 K 型假结）中的原子静电相互作用的收敛行为。
