In Silico Investigation of Lactone and Thiolactone Inhibitors in Bacterial Quorum Sensing Using Molecular Modeling

Abstract

In the present study, the origin of the anti-quorum sensing (QS) activities of several members of a two recently synthesized and in vitro tested classes of lactone and thiolactone based inhibitors were computationally investigated. Docking and molecular dynamic (MD) simulations and binding free energy calculations were carried out to reveal the exact binding and inhibitory profiles of these compounds. The higher in vitro inhibitory activity of the lactone based inhibitors relative to their thiolactone isosteres was verified based on estimating the binding energies, the docking scores and monitoring the stability of the complexes produced in the MD simulations. The strong electrostatic contribution to the binding energies may be responsible for the higher inhibitory activity of the lactone with respect to the thiolactone series. The results of this study help to understand the anti-QS properties of lactone-based inhibitors and provide important information that may assist in the synthesis of novel QS inhibitors.