In silico investigation of lactone and thiolactone inhibitors in bacterial quorum sensing using molecular modeling

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 antiQS properties of lactone-based inhibitors and provide important information that may assist in the synthesis of novel QS inhibitors. Suggested Reviewers: Chang-Guo Zhan, Professor College of Pharmacy, University of Kentuc [email protected] Jaime Rubio-Martinez, Professor Universitat de Barcelona (UB) and the Institut de Recerca en Química Teòrica i Computacional (IQTCUB), Martí i Franqués 1, 08028, Barcelona, Spain [email protected] Prasad V. Bharatam, Professor National Institute of Pharmaceutical Education and Research (NIPER), Sector-67, S. A. S. Nagar, 160 062, Punjab, India [email protected] Dawei Zhang School of Physical and Mathematical Sciences, Nanyang Technological University, Singapore, 637371, Singapore Powered by Editorial Manager® and Preprint Manager® from Aries Systems Corporation