Deciphering the interaction of perampanel and calf thymus DNA: A multi-spectroscopic and computer modelling study

• Published in: Journal of molecular structure Vol. 1270; p. 133900
• Main Authors: Lei, Yating, Zhang, Zihang, Ma, Xiulan, Cai, Ruirui, Dai, Lulu, Guo, Ying, Tuo, Xun
• Format: Journal Article
• Language: English
• Published: Elsevier B.V 15.12.2022
• Subjects: Binding behavior; Calf thymus DNA; Dynamic properties; Molecular docking; Perampanel; Dynamic properties; Binding behavior; Calf thymus DNA; Perampanel; Molecular docking
• ISSN: 0022-2860; 1872-8014
• DOI: 10.1016/j.molstruc.2022.133900

•PER bound with ctDNA to form a binary complex.•Hydrogen bonds and van der Waals force worked in the binding process.•PER embedded in the ctDNA minor groove rich of A-T bases.•PER-DNA system equilibrated after 100 ns.•DC-9, DT-19, and DT-20 contributed a lot to stabilizing PER-DNA complex. Perampanel (PER) is the first drug to treat epilepsy by blocking α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors. In the current study, the interaction of PER and calf thymus DNA (ctDNA) was explored through various spectroscopic techniques and computer modelling. According to the UV-vis titration results, PER combined with ctDNA via groove binding, which was also confirmed by thermal melting, salt effect, ssDNA/dsDNA quenching, and competitive experiments. The dominant forces were hydrogen bond and van der Waals force. And the binding constant obtained was 6.97 × 103 M−1 at 298 K. According to the data from FTIR assays and computer modelling, PER was embedded in the minor groove of ctDNA rich in A and T bases. In the simulation of 200 ns, the PER-DNA system reached equilibrium at about 100 ns. The structure of DNA became loose when a stable binary complex with PER was formed. The energy decomposition indicated that DC-9, DT-19, and DT-20 bases played a main role in this complex-forming. In summary, this study contributed to understanding the interaction mechanism of PER and ctDNA. [Display omitted]