Interaction mechanism between hydroxychloroquine sulfate and collagen: Insights from multi-spectroscopy, molecular docking, and molecular dynamic simulation methods

Abstract

Hydroxychloroquine sulfate (HCQ) can be used to treat various connective tissue diseases. Collagen, which is not only an important drug delivery carrier but also the main component in the connective tissue, is the focus of this study. Here, the interaction mechanism of HCQ with collagen was investigated through various spectroscopic and computational methods. It is found that HCQ binds to collagen spontaneously, primarily via hydrophobic interactions and some hydrogen bonds. The findings of X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FTIR) and scanning electron microscopy (SEM) verified that formation of HCQ-collagen complex and the amorphous structure, secondary structures, and microstructure of collagen were changed after HCQ binding. A decrease in the relaxation time of free water was observed in the collagen system when HCQ was added. Molecular docking demonstrated that HCQ was almost buried in the cavity of collagen via some hydrophobic interactions with one hydrogen bond, which conforms to the findings of the fluorescence and FTIR analyses. Molecular dynamic (MD) simulations further revealed the structural change information in the docking process. Hopefully, the information generated in this study can provide some useful insights for the research on the pharmacological mechanisms of HCQ in the treatment of the connective tissue diseases and the application of collagen as a drug carrier.