In Silico Screening of Quorum Sensing Inhibitor Candidates Obtained by Chemical Similarity Search

Quorum sensing (QS) is a bacterial communication using signal molecules, by which they sense population density of their own species, leading to group behavior such as biofilm formation and virulence. Autoinducer-2 (AI2) is a QS signal molecule universally used by both gram-positive and gram-negative bacteria. Inhibition of QS mediated by AI2 is important for various practical applications, including prevention of gum-disease caused by biofilm formation of oral bacteria. In this research, molecular docking and molecular dynamics (MD) simulations were performed for molecules that are chemically similar to known AI2 inhibitors that might have a potential to be quorum sensing inhibitors. The molecules that form stable complexes with the AI2 receptor protein were found, suggesting that they could be developed as a novel AI2 inhibitors after further in vitro validation. The result suggests that combination of ligand-based drug design and computational methods such as MD simulation, and experimental verification, may lead to development of novel AI inhibitor, with a broad range of practical applications.