Spectroscopic methodologies and molecular docking studies on the interaction of the soluble guanylate cyclase stimulator riociguat with human serum albumin

• Published in: BioScience Trends Vol. 12; no. 4; pp. 369 - 374
• Main Authors: Ma, Rui, Li, Zhenyu, Di, Xiaxia, Guo, Dongxiao, Ji, Jianbo, Wang, Shuqi
• Format: Journal Article
• Language: English
• Published: Japan International Research and Cooperation Association for Bio & Socio-Sciences Advancement 31.08.2018
• Subjects: Binding Sites; human serum albumin (HSA); Humans; interaction; molecular docking; Molecular Docking Simulation; Pyrazoles - chemistry; Pyrimidines - chemistry; Riociguat; Serum Albumin, Human - chemistry; Serum Albumin, Human - metabolism; Thermodynamics; interaction; molecular docking; human serum albumin (HSA); Riociguat
• ISSN: 1881-7815; 1881-7823
• DOI: 10.5582/bst.2018.01081

Interaction of riociguat with human serum albumin (HSA) is extremely important in understanding the drug's disposition and efficiency. In the current study, the binding of riociguat to HSA was explored using spectroscopic methods and molecular docking. The quenching constant, the binding constant, the number of binding sites, thermodynamic parameters, and the secondary structure of protein were determined. A fluorescence study revealed that riociguat quenched HSA fluorescence via static quenching with a binding constant of 1.55 × 104 L mol-1 at 298 K. The calculated thermodynamic parameters indicated that the binding process was spontaneous and that the main interaction force was hydrophobic interaction. Site marker competitive binding experiments and molecular docking studies suggested that riociguat was inserted into the subdomain IIA (site I) of HSA. Alterations in the protein secondary structure after drug complexation were predicted. Results indicated that the protein a-helix structure increased with an increasing concentration of riociguat. This indicated that a riociguat-HSA complex was formed and that the protein secondary structure was altered by the addition of riociguat.