Bhai Surjit, Ganguly Bishwajit
Computation and Simulation Unit (Analytical and Environmental Science Division and Centralized Instrument Facility), CSIR-Central Salt and Marine Chemicals Research Institute Bhavnagar Gujarat India-364 002
Academy of Scientific and Innovative Research (AcSIR) Ghaziabad 201002 Uttar Pradesh India.
RSC Adv. 2020 Nov 10;10(67):40969-40982. doi: 10.1039/d0ra07526d. eCollection 2020 Nov 9.
Metal-mediated base pairs have attracted attention in nucleic acid research and molecular devices. Herein, we report a systematic computational study on Hg-mediated base pairs with canonical and TT mispair dimers. The computed results revealed that the model TT (thymine-thymine with DNA backbone) mispair is more energetically favored than the canonical base pairs. The TTTT mispair dimer is more energetically stable by ∼36.0 kcal mol than the corresponding canonical ATGC base pairs. The Hg⋯Hg metallophilic interaction was observed with the TTTT mispair and not the canonical base pairs. The ATGC (adenine: thymine, guanine: cytosine) base pairs were significantly perturbed upon interaction with the mercury ion; however, the TTTT mispairs were aligned upon interaction with the Hg ion. The TTTT mispair adopts a B-type conformation with proper alignment of its nucleobases along the axis. The MESP calculations showed a larger value for the interacting nitrogen centers of the thymine nucleobase, supporting its stronger binding with the Hg ion compared to the other nucleobases. The role of the backbone is crucial in nucleic acids to determine many useful properties, and PNAs have been exploited extensively in the literature. Thus, this study was further extended to metal-mediated PNA-containing dimer mispairs such as TTTT (thymine-thymine dimer model with hybrid DNA and PNA backbone) and TTTT (thymine-thymine dimer model with PNA backbone). The calculated results showed that the TTTT PNA mispair is thermodynamically more stable than the canonical dimers. The enthalpy calculated for TTTT and TTTT at the B3LYP-D3/6-31G* level of theory showed that TTTT is ∼3.0 kcal mol more stable than TTTT. The metallophilic interaction of Hg ions in the TTTT mispair was not observed; however, the metal ions interact with the nitrogen of the thymine bases, presumably enhancing the stability of this mispair by strong electrostatic interactions. These interactions arise due to the P-type conformations of PNAs, which lack metallophilic interactions between the metal ions and can adopt a wider and more unwounded helix. The interaction of the mispair dimers with the explicit water molecules also showed a similar stability trend to that observed with the implicit solvation model. The metallophilic interaction (Hg⋯Hg) was found to be conserved in TTTT. The AIM analysis performed for these dimers revealed that the interactions are primarily electrostatic in nature. The UV-vis absorption spectra of the mispair systems calculated at the B3LYP-D3/6-31G* level of theory using the TD-DFT method in the aqueous phase suggested that the absorption maximum is located at a longer wavelength in the case of TTTT compared to the corresponding TTTT and can be a signature to identify the formation of metal-mediated nucleic acid systems.
金属介导的碱基对在核酸研究和分子器件中受到了关注。在此，我们报告了一项关于汞介导的碱基对与标准碱基对及TT错配二聚体的系统计算研究。计算结果表明，模型TT（带有DNA骨架的胸腺嘧啶 - 胸腺嘧啶）错配比标准碱基对在能量上更有利。TTTT错配二聚体比相应的标准ATGC碱基对在能量上更稳定约36.0千卡/摩尔。在TTTT错配中观察到了Hg⋯Hg亲金属相互作用，而标准碱基对中未观察到。ATGC（腺嘌呤：胸腺嘧啶，鸟嘌呤：胞嘧啶）碱基对在与汞离子相互作用时受到显著扰动；然而，TTTT错配在与Hg离子相互作用时会排列整齐。TTTT错配采用B型构象，其核碱基沿轴正确排列。MESP计算表明，胸腺嘧啶核碱基相互作用的氮中心具有更大的值，这表明与其他核碱基相比，它与Hg离子的结合更强。骨架在核酸中对于确定许多有用性质至关重要，并且肽核酸（PNA）在文献中已被广泛研究。因此，本研究进一步扩展到金属介导的含PNA的二聚体错配，如TTTT（具有混合DNA和PNA骨架的胸腺嘧啶 - 胸腺嘧啶二聚体模型）和TTTT（具有PNA骨架的胸腺嘧啶 - 胸腺嘧啶二聚体模型）。计算结果表明，TTTT PNA错配比标准二聚体在热力学上更稳定。在B3LYP - D3/6 - 31G理论水平下计算的TTTT和TTTT的焓表明，TTTT比TTTT稳定约3.0千卡/摩尔。在TTTT错配中未观察到Hg离子的亲金属相互作用；然而，金属离子与胸腺嘧啶碱基的氮相互作用，推测通过强静电相互作用增强了这种错配的稳定性。这些相互作用是由于PNA的P型构象引起的，PNA在金属离子之间缺乏亲金属相互作用，并且可以采用更宽且更无扭曲的螺旋。错配二聚体与明确水分子的相互作用也显示出与隐式溶剂化模型观察到的类似稳定性趋势。在TTTT中发现亲金属相互作用（Hg⋯Hg）是保守的。对这些二聚体进行的AIM分析表明，相互作用主要是静电性质的。在水相中使用TD - DFT方法在B3LYP - D3/6 - 31G理论水平下计算的错配系统的紫外 - 可见吸收光谱表明，与相应的TTTT相比，TTTT的吸收最大值位于更长波长处，并且可以作为识别金属介导的核酸系统形成的标志。
