Insights into the binding properties of calf thymus DNA with lopinavir from spectroscopic and computational studies

• Published in: Journal of molecular liquids 2021-04, Vol.328, p.115491, Article 115491
• Main Authors: Kou, Song-Bo, Zhou, Kai-Li, Lin, Zhen-Yi, Lou, Yan-Yue, Shi, Jie-Hua, Liu, Ying-Xin
• Format: Article
• Language: English
• Subjects: Binding mode; Calf thymus DNA; Docking; Lopinavir; Spectroscopy
• ISSN: 0167-7322; 1873-3166
• DOI: 10.1016/j.molliq.2021.115491

Lopinavir (LPV), an important antiviral drug, can inhibit effectively wild type and mutant HIV protease. In this work, molecular interaction mechanism between LPV and calf thymus deoxyribonucleic acid (ct-DNA) was characterized by spectroscopic, viscosity and molecular docking approaches to attain some important information about the LPV-ct-DNA interaction including binding affinity, binding mode, main driving-forces and structural change of ct-DNA. UV–vis titration data demonstrated that the LPV-ct-DNA complex was formed, and the binding affinity under the studied conditions was weak due to the binding constant at the level of 103 M−1. The negative values of ΔH0 (−26.63 kJ∙mol−1) and ΔS0 (−24.11 J∙mol−1∙K−1) revealed that hydrogen bonding and Van der Waals forces played an indispensable part in the LPV-ct-DNA complexation process. The outcomes from viscosity measurements excluded the possibility of intercalation mode between LPV and ct-DNA. The results from UV–vis titration experiments, displacement experiments and influence of ionic strength indicated that LPV bound to the minor groove of ct-DNA, which was further confirmed by docking studies. Besides, a minor change in the conformation of ct-DNA can be observed from CD spectral analysis. Our studies scientifically elucidated the binding behavior between LPV and ct-DNA for the first time and were beneficial to assessing the pharmacological properties of this antiviral drug. [Display omitted] •Binding characteristics of Lopinavir with ct-DNA was expounded.•Lopinavir bound to minor groove of ct-DNA and forms 1:1 complex.•Dominate interacting forces were hydrogen bonding and van der Waals force.•Interaction between the two resulted in the slight alteration in the DNA conformation.