Binding mechanism of 4−octylphenol with human serum albumin: Spectroscopic investigations, molecular docking and dynamics simulation

Abstract

4−Octylphenol (OP) is an environmental estrogen that can enter organisms through the food chain and cause various toxic effects. Here, the interaction between OP and human serum albumin (HSA) was explored through multipectral, molecular docking and dynamics simulation. The results showed that OP and HSA formed a ground state complex through a static quenching mechanism, and the interaction was spontaneously driven by hydrogen bonds and hydrophobic interaction forces. The binding constant at different temperatures was measured to be on the order of 105 L mol−1. Site competition experiments suggested that OP interacted with amino acid residues Lys195, Cy245 and Cys246 located at the Sudlow site I of HSA, resulting in a more stretched protein peptide. The presence of OP increased the surface hydrophobicity of HSA, and reduced the content of α-helix in HSA by 3.4%. FT−IR spectra showed that OP interacted with the C=O and C-H groups of the polypeptide backbone. Molecular docking demonstrated that OP mainly bound to Site I of HSA and hydrogen bonds participated in the interaction. In addition, molecular dynamics simulations further explored the stability and dynamic behavior of the OP−HSA complex through RMSD, RMSF, SASA and Rg.