Department of Chemistry and Biochemistry, University of Lethbridge, 4401 University Drive, Lethbridge, Alberta T1K 3M4, Canada.
J Phys Chem B. 2010 Mar 11;114(9):3355-67. doi: 10.1021/jp911990g.
Previous computational studies have examined pi-pi and pi(+)-pi stacking and T-shaped interactions in nucleobase-amino acid dimers, yet it is important to investigate how additional amino acids affect these interactions since simultaneous contacts often appear in nature. Therefore, this paper investigates the geometries and binding strengths of amino acid-nucleobase-amino acid trimers, which are compared to the corresponding nucleobase-amino acid dimer interactions. We concentrate on systems containing the natural nucleobase adenine or its (cationic) damaged counterpart, 3-methyladenine, and the aromatic amino acid histidine, in both the neutral and protonated forms. This choice of molecules provides information about pi-pi and pi(+)-pi stacking and T-shaped interactions in asymmetric, biologically relevant systems. We determined that both stacked and T-shaped interactions, as well as both pi-pi and pi(+)-pi interactions, exhibit geometric additivity. To investigate the energetic additivity in our trimers, the synergy (E(syn)) and the additivity (E(add)) energy were examined. E(add) reveals that it is important to consider the interaction between the two amino acids when examining the additivity of nucleobase-amino acid interactions. Additionally, E(syn) and E(add) indicate that pi(+)-pi interactions are quite different from pi-pi interactions. The magnitude of E(add) is generally less than 2 kJ mol(-1), which suggests that these interactions are additive. However, the interaction energy analysis does not provide information about the individual interactions in the trimers. Therefore, the quantum theory of atoms in molecules (QTAIM) was implemented. We find inconsistent conclusions from our QTAIM analysis and interaction energy evaluation. However, the magnitudes of the differences between the dimer and trimer critical point properties are extremely small and therefore may not be able to yield conclusive descriptions of differences (if any) between the dimer and trimer interactions. We hypothesize that, due to the limited number of investigations of this type, it is currently unclear how QTAIM can improve our understanding of pi-pi and pi(+)-pi dimers and trimers. Therefore, future work must systematically alter the pi-pi or pi(+)-pi system to definitively determine how the geometry, symmetry, and system size alter the QTAIM analysis, which can then be used to understand biologically relevant complexes.
先前的计算研究已经考察了碱基-氨基酸二聚体中的 pi-pi 和 pi(+)-pi 堆积以及 T 型相互作用，但研究额外的氨基酸如何影响这些相互作用很重要，因为这些相互作用在自然界中经常同时出现。因此，本文研究了氨基酸-碱基-氨基酸三聚体的几何形状和结合强度，并将其与相应的碱基-氨基酸二聚体相互作用进行了比较。我们专注于包含天然碱基腺嘌呤或其（阳离子）受损对应物 3-甲基腺嘌呤以及芳香族氨基酸组氨酸的系统，这些系统既可以是中性形式，也可以是质子化形式。这些分子的选择提供了关于不对称、生物学相关系统中 pi-pi 和 pi(+)-pi 堆积和 T 型相互作用的信息。我们确定，堆叠和 T 型相互作用以及 pi-pi 和 pi(+)-pi 相互作用都表现出几何加和性。为了研究我们三聚体中的能量加和性，检查了协同能 (E(syn)) 和加和能 (E(add))。E(add) 表明，在研究碱基-氨基酸相互作用的加和性时，考虑两个氨基酸之间的相互作用很重要。此外，E(syn) 和 E(add) 表明 pi(+)-pi 相互作用与 pi-pi 相互作用有很大不同。E(add) 的大小通常小于 2 kJ mol(-1)，这表明这些相互作用是加和的。然而，相互作用能分析并不能提供三聚体中各个相互作用的信息。因此，我们实施了量子原子分子理论 (QTAIM)。我们从 QTAIM 分析和相互作用能评估中得出不一致的结论。然而，二聚体和三聚体临界点性质之间的差异大小非常小，因此可能无法对二聚体和三聚体相互作用之间的差异（如果存在）得出明确的描述。我们假设，由于对此类研究的数量有限，目前尚不清楚 QTAIM 如何能够提高我们对 pi-pi 和 pi(+)-pi 二聚体和三聚体的理解。因此，未来的工作必须系统地改变 pi-pi 或 pi(+)-pi 系统，以明确确定几何形状、对称性和系统大小如何改变 QTAIM 分析，然后可以利用该分析来理解与生物学相关的复合物。
