Modulation of protein-ligand interactions in the presence of ZIF-8: Spectroscopy and molecular dynamics simulation

Abstract

In this paper, we investigated the protein-ligand interactions in the presence of ZIF-8 using multi-spectroscopic approaches and molecular dynamics simulation. Fluorescence experiments and molecular docking results showed that ZIF-8 did not change the type of quenching and interaction force between ciprofloxacin (CIP) and human serum albumin (HSA), but made the binding constant of HSA-CIP to be smaller, suggesting that ZIF-8 maybe accelerate the dissociation of CIP from HSA-CIP complex. Moreover, the effect of ZIF-8 on the physiological function of HSA was explored. Multi-spectroscopic methods revealed that ZIF-8 did not significantly alter the microenvironment of amino acid groups, but cause a slight decrease in the content of α-helical conformation, and a sparse and flexible structure of the protein backbone. These peculiarities might lead to the diminution of HSA's ability to control drugs. In short, ZIF-8 might enhance drug effect due to affecting the binding of drugs to proteins. However, the present study is only a preliminary investigation of the suitability of ZIF-8 as a drug carrier in vitro, and subsequent in vivo experimental studies will be required to further confirm the idea.

Keywords: Ciprofloxacin; Drug carrier; Human serum albumin; Molecular dynamics simulation; Spectroscopy; ZIF-8.