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Comprehensive views toward the biomolecular recognition of an anticancer drug, leflunomide with human serum albumin.

Md Zahirul KabirHafsa TayyabCem ErkmenSaharuddin B MohamadBengi Uslu
Published in: Journal of biomolecular structure & dynamics (2023)
Biomolecular association of an anticancer drug, leflunomide (LEF) with human serum albumin (HSA), the leading ligands carrier in human circulation was characterized using biophysical ( i.e., fluorescence, absorption and voltammetric) methods and computational ( i.e., molecular docking and molecular dynamics simulation) techniques. Evaluations of fluorescence, absorption and voltammetric findings endorsed the complex formation between LEF and HSA. An inverse relationship of Stern-Volmer constant-temperature and hyperchromic shift of the protein's absorption signal with addition of LEF confirmed the LEF quenched the HSA fluorescence through static process. Moderate nature of binding strength (binding constant = 2.76-4.77 × 10 4 M -1 ) was detected towards the LEF-HSA complexation, while the association process was naturally driven via hydrophobic interactions, van der Waals interactions and hydrogen bonds, as evident from changes in entropy (Δ S = + 19.91 J mol -1 K -1 ) and enthalpy (Δ H = - 20.09 kJ mol -1 ), and molecular docking assessments. Spectral analyses of synchronous and three-dimensional fluorescence validated microenvironmental fluctuations near Trp and Tyr residues upon LEF binding to the protein. LEF association with HSA significantly defended temperature-induced destabilization of the protein. Although LEF was found to attach to HSA at Sudlow's sites I and II, but exhibited greater preference toward its site I, as detected by the investigations of competitive site-marker displacement. Molecular dynamics simulation assessment revealed that the complex attained equilibrium throughout simulations, showing the LEF-HSA complex constancy.Communicated by Ramaswamy H. Sarma.
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