Insights into the binding mechanism of a model protein with fomesafen: Spectroscopic studies, thermodynamics and molecular modeling exploration

Abstract The long residual period and toxicity of fomesafen makes it accumulating in the environment as environmental pollutant. Bovine serum albumin (BSA) plays an indispensable role in the binding, trans-mission, distribution and efficacy of fomesafen in vivo. Thereby, we studied the interaction of fomesafen and BSA by spectroscopic methods and molecular simulation. Spectroscopic measurements reveal that static quenching is the predominant quenching mechanism, resulting in the forming of BSA-fomesafen. The thermodynamic results manifest that hydrophobic force is the major factor. We have found an active pocket around Trp-213 based on competitive binding of fomesafen and warfarin. The model optimized by MD is the ultimately identified model reflecting real situation, from which we can find that the interactions of BSA-fomesafen depend mainly on the contribution of hydrophobic residues. Compared with the models before and after MD, we have found that aqueous solution is an indispensable condition for the emergence of significant hydrophobic interaction in this system. The free energy and energy decomposition measured by the MD simulations indicate that the interaction is spontaneous and Trp-213 has great contributions to the formation of BSA-fomesafen system. In summary, our results have pro-vided meaningful reference to assess the biological toxicity risk of fomesafen.