Mechanistic Insights from Docking and Dynamics: Soy Isoflavonoids Disrupt P. Aeruginosa Quorum Sensing by Targeting AHL Synthase LasI

Abstract

Abstract

Multidrug-resistant specially in Pseudomonas aeruginosa is an emerging global health threat; thus, there is an increasing demand for anti-virulence strategies targeting bacterial communication rather than their growth. As a central enzyme in the quorum-sensing network, the LasI AHL synthase is a promising anti-virulence target. Thus, this work aimed at investigating the inhibitory potential of three soy isoflavonoids, namely genistein, daidzein, and glycitein, against LasI AHL synthase by using an integrated in silico approach that included molecular docking, molecular dynamics simulations. While docking predicted genistein as the strongest binder, MD analyses evidenced that genistein showed increased structural stability and maintained more consistent interaction patterns within the LasI synthase active site. MM/PBSA results pointed toward genistein as the most energetically favorable ligand. Therefore, this study positions genistein as a promising scaffold for the development of anti-quorum sensing drugs that should be experimentally validated.