Biomolecular interaction of a platelet aggregation inhibitor, 3,4-methylenedioxy-β-nitrostyrene with human serum albumin: multi-spectral and computational characterization

Abstract

Molecular interaction of the 3,4-methylenedioxy-β-nitrostyrene (MNS), an inhibitor of platelet aggregation with the main transport protein, albumin from human serum (HSA) was explored using absorption, fluorescence and circular dichroism (CD) spectroscopy in combination with in silico analyses. The MNS–HSA complexation was corroborated from the fluorescence and absorption spectral results. Implication of static quenching mechanism for MNS–HSA system was predicted from the Stern–Volmer constant, K_SV-temperature relationship as well as the bimolecular quenching rate constant, k_q values. Stabilization of the complex was affirmed by the value of the binding constant (K_a = 0.56-1.48 × 10⁴ M⁻¹). Thermodynamic data revealed that the MNS–HSA association was spontaneously driven mainly through hydrophobic interactions along with van der Waal’s interaction and H-bonds. These results were well supported by in silico interpretations. Far-UV and near-UV CD spectral results manifested small variations in the protein’s secondary and tertiary structures, respectively, while three-dimensional fluorescence spectra displayed microenvironmental fluctuations around protein’s fluorophores, upon MNS binding. Significant improvement in the protein’s thermostability was evident from the temperature-stability results of MNS-bound HSA. Binding locus of MNS, as identified by competitive drug displacement findings as well as in silico analysis, was found to be located in subdomain IIA (Sudlow’s site I) of the protein.

Communicated by Ramaswamy H. Sarma

Keywords:

• 3,4-methylenedioxy-β-nitrostyrene
• human serum albumin
• ligand–protein interaction
• fluorescence
• in silico analysis

Acknowledgments

The authors thank the Dean, Faculty of Science and the Head, Institute of Biological Sciences, Universiti Malaya for providing necessary facilities.

Disclosure statement

No potential conflict of interest was reported by the authors.

Additional information

Funding

This work was finacially supported by the University of Malaya Frontier Science Research Cluster (FRSC) [Frontier Research Grant (FRG) 2017 (FG025-17AFR)]. Md. Zahirul Kabir gratefully acknowledges financial assistance from the University of Malaya in the form of post-doctoral research fellowship.