Molecular simulation study of the specific combination between four kinds of phthalic acid esters and human serum albumin

• The binding site was confirmed by MD simulation and experiment together.
• MD simulation showed that HSA and HSA–PAEs complexes were stabilized around 4 ns.
• The HSA–PAEs has conformational change compared with HSA only.
• Experimental and theoretical results correspond highly with each other.
• This mechanism revealed could provide theoretical basis for further study.

The interaction between endocrine disruptor phthalic acid esters (PAEs) and human serum albumin (HSA) was studied by fluorescence spectroscopy and molecular modeling methods. The efficiency of energy transfer and the distance between HSA and PAEs were calculated. The results showed that all of the four kinds of PAEs could quench the intrinsic fluorescence of the HSA, with the mechanisms of static quenching and non-radiative energy transfer. Molecular docking study and thermodynamic analysis revealed that the binding behavior was mainly governed by hydrophobic force. And the results of site marker competitive experiments and modeling method suggested that the four PAEs would mainly bind to the HSA in sub-domain IIIA, which demonstrated that the experimental results could coordinate with the theoretical results. Molecular dynamic simulation (MD) revealed that HSA did have a slight conformational change when it bound with PAEs. It also verified the greater stability of HSA–PAEs complex compared to free protein.