Computational studies of LasR

NAISS 2023/5-489


NAISS Medium Compute

Principal Investigator:

Elena Vikström


Linköpings universitet

Start Date:


End Date:


Primary Classification:

10601: Structural Biology

Secondary Classification:

10407: Theoretical Chemistry

Tertiary Classification:

30103: Medicinal Chemistry



Our research focuses on the discovery of new small molecule inhibitors of quorum sensing-mediate signalling in Pseudomonas aeruginosa. Quorum sensing (QS) is a bacterial cell-to-cell communication that controls virulence and biofilm formation of opportunistic pathogens (e.g., Pseudomonas aeruginosa). Inhibition of the QS-mediated signaling in P. aeruginosa represents an effective approach to attenuate infecting bacteria. Las is one of the three major QS systems in P. aeruginosa, where the receptor protein LasR up-regulates genes associated with virulence and biofilm formation upon activation by a cognate autoinducer. Inhibition of LasR by small molecules represents a promising strategy to attenuate bacterial virulence. We have developed a series of new small molecules that were experimentally determined to limit the activity of LasR. Our goals are to improve the understanding of the interactions between LasR and these ligands at the atomic level, and design new inhibitors. We will use structure-based computational methods to first predict the binding mode between our ligands and LasR. Predicted binding modes will then be used as starting point to design new compounds and perform virtual screening campaigns by molecular docking, similarity-based searches, and machine-learning approaches. New computational strategies will be also developed to enhance the discovery of LasR inhibitors. Candidates from the simulations will be experimentally tested in our lab. Our current research is funded by the Petrus and Augusta Hedlund Foundation, and the Faculty of Medicine and Health Sciences, Linköping University.