Schneider Amelia L, Albrecht Amanda V, Huang Kenneth, Germann Markus W, Poon Gregory M K
Department of Chemistry, Georgia State University, Atlanta, GA 30303, USA.
Department of Biology, Georgia State University, Atlanta, GA 30303, USA.
Life (Basel). 2022 Apr 30;12(5):666. doi: 10.3390/life12050666.
Fixed-charge (non-polarizable) forcefields are accurate and computationally efficient tools for modeling the molecular dynamics of nucleic acid polymers, particularly DNA, well into the µs timescale. The continued utility of these forcefields depends in part on expanding the residue set in step with advancing nucleic acid chemistry and biology. A key step in parameterizing new residues is charge derivation which is self-consistent with the existing residues. As atomic charges are derived by fitting against molecular electrostatic potentials, appropriate structural models are critical. Benchmarking against the existing charge set used in current AMBER nucleic acid forcefields, we report that quantum mechanical models of deoxynucleosides, even at a high level of theory, are not optimal structures for charge derivation. Instead, structures from molecular mechanics minimization yield charges with up to 6-fold lower RMS deviation from the published values, due to the choice of such an approach in the derivation of the original charge set. We present a contemporary protocol for rendering self-consistent charges as well as optimized charges for a panel of nine non-canonical residues that will permit comparison with literature as well as studying the dynamics of novel DNA polymers.
固定电荷（不可极化）力场是用于模拟核酸聚合物（尤其是DNA）长达微秒时间尺度分子动力学的准确且计算高效的工具。这些力场的持续实用性部分取决于随着核酸化学和生物学的发展逐步扩展残基集。为新残基参数化的关键步骤是电荷推导，它要与现有残基保持自洽。由于原子电荷是通过拟合分子静电势推导出来的，所以合适的结构模型至关重要。通过与当前AMBER核酸力场中使用的现有电荷集进行基准测试，我们发现脱氧核苷的量子力学模型，即使在高理论水平下，也不是用于电荷推导的最佳结构。相反，分子力学最小化得到的结构所产生的电荷与已发表值的均方根偏差低至6倍，这是因为在原始电荷集推导中选择了这种方法。我们提出了一种当代协议，用于为一组九个非规范残基生成自洽电荷以及优化电荷，这将允许与文献进行比较，并研究新型DNA聚合物的动力学。
