Please, check our recent publication in Molecules (IF 3.267):
Identification of New Potential Inhibitors of Quorum Sensing through a Specialized Multi-Level Computational Approach
Molecules | DOI: 10.3390/molecules26092600
Biofilms are aggregates of microorganisms anchored to a surface and embedded in a self-produced matrix of extracellular polymeric substances and have been associated to 80% of all bacterial infections in humans. Because bacteria in biofilms are less amenable to antibiotic treatment, biofilms have been associated to the development of antibiotic resistance, a problem that urges the development of new therapeutic options and approaches. Interfering with quorum sensing (QS), an important process of cell-to-cell communication by bacteria in biofilms is a promising strategy to inhibit biofilm formation and development.
Here we describe and apply an in silico computational protocol for the identification of novel quorum sensing inhibitors, using CviR- the quorum sensing receptor from Chromobacterium violaceum – as a model target.
This in silico approach combines protein-ligand docking (with 7 different docking programs/scoring functions), receptor-based virtual screening, molecular dynamic simulations, and free energy calculations. Particular emphasis was dedicated to optimizing the discrimination ability between active/inactive molecules in virtual screening tests using a target-specific training set. Overall, the optimized protocol was used to evaluate 66461 molecules, including those on the ZINC/FDA Approved database and to the Mu.Ta.Lig Virtual Chemotheca. Multiple promising compounds were identified, yielding good prospects for future experimental validation and for drug repurposing towards QS inhibition.