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, 364 002, India.
Computation and Simulation Unit (Analytical and Environmental Science Division and Centralized Instrument Facility), CSIR-Central Salt and Marine Chemicals Research Institute, Bhavnagar, Gujarat, 364 002, India.
J Mol Graph Model. 2019 Dec;93:107445. doi: 10.1016/j.jmgm.2019.107445. Epub 2019 Aug 29.
Metal ion interaction with deoxyribonucleic acid and peptide nucleic acid were studied using B3LYP-D3/6-311++g(d,p)//B3LYP/6-31 + G(d) level of theory in aqueous phase employing polarized continuum (PCM) model. This study reports the role of backbones on deoxyribonucleic acid and peptide nucleic acid for complexation with different metal ions. The systematic study performed with DFT calculations reveals that central binding (Type-4) shows the strongest binding compared to the other binding modes because of the involvement of the backbone as well as the nitrogenous bases. The charged backbone of DNA nucleotides contributes significantly towards binding with the metal ions. The deoxyguanosine monophosphate (dGMP) clearly indicates the strongest binding upon complexation with Mg (-49.6 kcal/mol), Zn (-45.3 kcal/mol) and Cu (-148.4 kcal/mol), respectively. The neutral backbone of PNA also assists to complex the metal ions with PNA nucleotides. The Mg and Cu prefer to bind with the PNA-Cytosine (-32.9 kcal/mol & -132.9 kcal/mol) in central binding mode (type-4). PNA-Adenine-Zn (-29.1 kcal/mol) is the preferred binding mode (type-4) compared to other modes of interaction for this metal ion with PNA-Adenine nucleotide. The Cu ion showed the superior complexation ability with deoxyribonucleic acid and peptide nucleic acid compared to Mg and Zn ions. The cation-π complexation with the bases of nucleotides was also obtained with Cu ion. The AIM (atoms in molecule) theory has been applied to examine the nature of the interaction of Mg, Zn, and Cu ion to the deoxyribonucleic acid and peptide nucleic acid. The alkaline earth metal, Mg ion shows electrostatic nature while interaction with deoxyribonucleic acid and peptide nucleic acid, however, the transition metal ions (Zn, Cu) showed partly covalent nature as well with deoxyribonucleic acid and peptide nucleic acid. The optical properties calculated for the binding of metal ions with deoxyribonucleic acid and peptide nucleic acid showed a diagnostic signature to ascertain the interaction of metal ions with such nucleotides. Cu ion showed larger red shifts in the absorption spectrum values upon complexation with the DNAs and PNAs. The calculated results suggest that such metal ions would prefer to bind with the DNA compared to PNA in DNA-PNA duplexes. The preference for the binding of metal ions with DNA nucleotides is largely attributed to the contribution of charged backbones compared to the neutral PNA backbones.
在水相中采用极化连续介质（PCM）模型，使用B3LYP-D3/6-311++g(d,p)//B3LYP/6-31+G(d)理论水平研究了金属离子与脱氧核糖核酸和肽核酸的相互作用。本研究报告了脱氧核糖核酸和肽核酸的主链在与不同金属离子络合中的作用。通过密度泛函理论（DFT）计算进行的系统研究表明，由于主链以及含氮碱基的参与，中心结合（4型）与其他结合模式相比显示出最强的结合。DNA核苷酸带电荷的主链对与金属离子的结合有显著贡献。脱氧鸟苷单磷酸（dGMP）分别与Mg（-49.6 kcal/mol）、Zn（-45.3 kcal/mol）和Cu（-148.4 kcal/mol）络合时，清楚地表明了最强的结合。PNA的中性主链也有助于金属离子与PNA核苷酸络合。Mg和Cu在中心结合模式（4型）中更倾向于与PNA-胞嘧啶结合（-32.9 kcal/mol和-132.9 kcal/mol）。与该金属离子与PNA-腺嘌呤核苷酸的其他相互作用模式相比，PNA-腺嘌呤-Zn（-29.1 kcal/mol）是首选的结合模式（4型）。与Mg和Zn离子相比，Cu离子与脱氧核糖核酸和肽核酸表现出更强的络合能力。Cu离子还与核苷酸的碱基形成了阳离子-π络合。已应用分子中的原子（AIM）理论来研究Mg、Zn和Cu离子与脱氧核糖核酸和肽核酸相互作用的本质。碱土金属Mg离子与脱氧核糖核酸和肽核酸相互作用时表现出静电性质，然而，过渡金属离子（Zn、Cu）与脱氧核糖核酸和肽核酸相互作用时也表现出部分共价性质。计算得到的金属离子与脱氧核糖核酸和肽核酸结合的光学性质显示出一种诊断特征，以确定金属离子与此类核苷酸的相互作用。Cu离子与DNA和PNA络合时，吸收光谱值出现较大的红移。计算结果表明，在DNA-PNA双链体中，此类金属离子与DNA结合的倾向高于与PNA结合。金属离子与DNA核苷酸结合的偏好很大程度上归因于带电荷的主链与中性PNA主链相比的贡献。
