Modified nucleic acids have surged as a popular therapeutic route, emphasizing the importance of nucleic acid research in drug discovery and development. Beyond well-known RNA vaccines, antisense oligonucleotides and aptamers can incorporate various modified nucleic acids to target specific biomolecules for various therapeutic activities. Molecular dynamics simulations can accelerate the design and development of these systems with noncanonical nucleic acids by observing intricate dynamic properties and relative stability on the all-atom level. However, modeling these modified systems is challenging due to the time and resources required to parametrize components outside default force field parameters. Here, we present modXNA, a tool to derive and build modified nucleotides for use with Amber force fields. Several nucleic acid systems varying in size and number of modification sites were used to evaluate the accuracy of modXNA parameters, and results indicate the dynamics and structure are preserved throughout the simulations. We detail the protocol for quantum mechanics charge derivation and describe a workflow for implementing modXNA in Amber molecular dynamics simulations, which includes updates and added features to CPPTRAJ.

中文翻译：

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modXNA：用于琥珀力场的修饰核酸参数化的模块化方法


修饰核酸已成为一种流行的治疗途径，强调了核酸研究在药物发现和开发中的重要性。除了众所周知的 RNA 疫苗外，反义寡核苷酸和适配体还可以掺入各种修饰的核酸，以靶向特定的生物分子进行各种治疗活动。分子动力学模拟可以通过观察全原子水平上复杂的动力学特性和相对稳定性来加速这些具有非经典核酸的系统的设计与开发。然而，由于在默认力场参数之外对组件进行参数化需要时间和资源，因此对这些修改后的系统进行建模具有挑战性。在这里，我们介绍了 modXNA，这是一种用于 Amber 力场的衍生和构建修饰核苷酸的工具。使用几个大小和修饰位点数量不同的核酸系统来评估 modXNA 参数的准确性，结果表明在整个模拟过程中保留了动力学和结构。我们详细介绍了量子力学电荷推导的协议，并描述了在 Amber 分子动力学模拟中实现 modXNA 的工作流程，其中包括 CPPTRAJ 的更新和添加功能。