Sun Qiaomei, Suo Zili, Pu Hongyu, Tang Peixiao, Gan Na, Gan Ruixue, Zhai Yuanming, Ding Xiaohui, Li Hui
School of Chemical Engineering, Sichuan University Chengdu 610065 China
Analytical & Testing Center, Sichuan University Chengdu 610065 China
RSC Adv. 2018 Jun 4;8(36):20295-20303. doi: 10.1039/c8ra03702g. eCollection 2018 May 30.
Thiabendazole (TBZ) is a commonly used food preservative and has a wide range of anthelmintic properties. In this study, computer simulations and experiments were conducted to investigate the interaction mechanism of TBZ and herring sperm DNA (hsDNA) at the molecular level. Molecular docking showed that TBZ interacted with DNA in groove mode and bound in A-T and C-G base pair regions. Molecular dynamics (MD) was used to evaluate the stability of the TBZ-DNA complex and found that the three phases in MD and the hydrogen bonds helped maintain the combination. NMR relaxation indicated that TBZ had a certain affinity to hsDNA with a binding constant of 462.43 L mol, and the thiazole ring was the main group bound with DNA. Results obtained from fluorescence experiments showed that the binding of TBZ and hsDNA was predominantly driven by enthalpy through a static quenching mechanism. Circular dichroism and viscosity measurements proved the groove binding mode. The FTIR results clarified the conformational changes of DNA, that the DNA helix became shorter and compact, and the DNA structure transformed from B-form to A-form.
噻苯达唑（TBZ）是一种常用的食品防腐剂，具有广泛的驱虫特性。在本研究中，进行了计算机模拟和实验，以在分子水平上研究TBZ与鲱鱼精DNA（hsDNA）的相互作用机制。分子对接表明，TBZ以沟槽模式与DNA相互作用，并结合在A-T和C-G碱基对区域。分子动力学（MD）用于评估TBZ-DNA复合物的稳定性，发现MD中的三个阶段和氢键有助于维持结合。核磁共振弛豫表明，TBZ对hsDNA具有一定亲和力，结合常数为462.43 L/mol，噻唑环是与DNA结合的主要基团。荧光实验结果表明，TBZ与hsDNA的结合主要是通过焓驱动的静态猝灭机制。圆二色性和粘度测量证明了沟槽结合模式。傅里叶变换红外光谱（FTIR）结果阐明了DNA的构象变化，即DNA螺旋变短且紧凑，DNA结构从B型转变为A型。
