  In the present study, the origin of the anti-quorum sensing (QS) activities
of several members of a recently synthesized and in vitro tested class 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 activity of the lactone series
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.
