Department of Biomedical Engineering, The University of Texas at Austin, Austin, TX 78712, USA.
Interdisciplinary Life Sciences Graduate Program, The University of Texas at Austin, Austin, TX 78712, USA.
Molecules. 2024 Jul 10;29(14):3258. doi: 10.3390/molecules29143258.
Accurate calculation of non-covalent interaction energies in nucleotides is crucial for understanding the driving forces governing nucleic acid structure and function, as well as developing advanced molecular mechanics forcefields or machine learning potentials tailored to nucleic acids. Here, we dissect the nucleotides' structure into three main constituents: nucleobases (A, G, C, T, and U), sugar moieties (ribose and deoxyribose), and phosphate group. The interactions among these fragments and between fragments and water were analyzed. Different quantum mechanical methods were compared for their accuracy in capturing the interaction energy. The non-covalent interaction energy was decomposed into electrostatics, exchange-repulsion, dispersion, and induction using two ab initio methods: Symmetry-Adapted Perturbation Theory (SAPT) and Absolutely Localized Molecular Orbitals (ALMO). These calculations provide a benchmark for different QM methods, in addition to providing a valuable understanding of the roles of various intermolecular forces in hydrogen bonding and aromatic stacking. With SAPT, a higher theory level and/or larger basis set did not necessarily give more accuracy. It is hard to know which combination would be best for a given system. In contrast, ALMO EDA2 did not show dependence on theory level or basis set; additionally, it is faster.
准确计算核苷酸中的非共价相互作用能对于理解控制核酸结构和功能的驱动力以及开发针对核酸的先进分子力学力场或机器学习势至关重要。在这里，我们将核苷酸的结构分解为三个主要成分：碱基（A、G、C、T 和 U）、糖部分（核糖和脱氧核糖）和磷酸基团。分析了这些片段之间以及片段与水之间的相互作用。比较了不同的量子力学方法，以评估它们捕捉相互作用能的准确性。使用两种从头算方法：对称适应微扰理论（SAPT）和绝对局部分子轨道（ALMO），将非共价相互作用能分解为静电、交换排斥、色散和诱导。这些计算为不同的 QM 方法提供了基准，此外还提供了对氢键和芳构堆积中各种分子间力作用的有价值的理解。使用 SAPT，更高的理论水平和/或更大的基组并不一定能提供更高的准确性。很难知道哪种组合最适合给定的系统。相比之下，ALMO EDA2 不依赖于理论水平或基组；此外，它的速度更快。
