Native electrospray ionization mass spectrometry reveals the interaction variances between different bisphenol analogues and myoglobin

Abstract

Bisphenol analogues (BPs) are crucial industrial materials extensively utilized in the production of consumer goods. However, it is still unknown whether they will affect the structure of myoglobin (Mb) and cause adverse impacts. This study systematically investigates the interactions between eleven BPs and their structural analogs with Mb using native electrospray ionization mass spectrometry (native ESI-MS), and further verified their interaction by fluorescence spectroscopy (FLS), circular dichroism (CD), and molecular docking (MD). Specifically, native ESI-MS analysis revealed that four ligands form stable complexes with Mb, and their binding constants were quantitatively determined. Thermodynamic data derived from FLS and CD analyses indicated that ligand binding induces conformational changes in Mb by reducing its α-helix content. MD simulations further elucidated that the binding sites for these ligands are located near the heme pocket of Mb, involving key interactions including hydrogen bonding and hydrophobic forces. Structure-activity relationship analysis suggested that sulfonyl and hydroxyl groups play critical roles in the ligand-Mb binding, where hydrophobic atoms enhance binding affinity by increasing molecular hydrophobicity, and ortho-substituted hydroxyl groups significantly influence binding strength. The integration approaches provide valuable information for the design and toxicity assessment of those bisphenol analogues in environmental implications.