Functional magnetic nanoparticles combined with molecular dynamics technology to screen quorum sensing inhibitors from natural substances: Accuracy, efficiency and high throughput

Abstract

Using effective quorum sensing inhibitors (QSIs) is an important way to mitigate microbial contamination. The traditional QSI screening method is time-consuming and of low accuracy. To solve this, a more efficient and accurate method, ligand fishing-bound HPLC-MS-coupled molecular dynamics technology, was developed. In its early stages, Fe3O4@PS-ANTA-Ni2+ magnetic nanoparticles (MNPs) were prepared, to which the maximum adsorption rate of HalR (His-tag) protein was as high as 97.4%. Notably, Fe3O4@PS-ANTA-Ni2+ MNPs still exhibited good adsorption performance after being reused five times. Phytol was isolated from laurel extract by the functionalized MNPs due to its specific binding with HalR protein. To ensure the accuracy of phytol as QSI, molecular dynamics simulations were used to evaluate the specific binding between phytol and the HalR protein. The results showed that phytol has great potential as a QSI. Moreover, the subsequent quorum sensing verification experiments proved that phytol is an effective QSI. In summary, this work provides researchers with an efficient and accurate scheme for finding effective QSIs.