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Quorum sensing (QS) is a bacterial communication process mediated by both native and non-native small-molecule quorum sensing modulators (QSMs), many of which have been synthesized to disrupt QS pathways. While structure-activity relationships have been developed to relate QSM structure to the activation or inhibition of QS receptors, less is known about the transport mechanisms that enable QSMs to cross the lipid membrane and access intracellular receptors. In this study, we used atomistic MD simulations and an implicit solvent model, called COSMOmic, to analyze the partitioning and translocation of QSMs across lipid bilayers. We performed umbrella sampling at atomistic resolution to calculate partitioning and translocation free energies for a set of naturally occurring QSMs, then used COSMOmic to screen the water-membrane partition and translocation free energies for 50 native and non-native QSMs that target LasR, one of the LuxR family of quorum-sensing receptors. This screening procedure revealed the influence of systematic changes to head and tail group structures on membrane partitioning and translocation free energies at a significantly reduced computational cost compared to atomistic MD simulations. Comparisons with previously determined QSM activities suggest that QSMs that are least likely to partition into the bilayer are also less active. This work thus demonstrates the ability of the computational protocol to interrogate QSM-bilayer interactions which may help guide the design of new QSMs with engineered membrane interactions.