Diptool-A Novel Numerical Tool for Membrane Interactions Analysis, Applying to Antimicrobial Detergents and Drug Delivery Aids.

The widespread problem of resistance development in bacteria has become a critical issue for modern medicine. To limit that phenomenon, many compounds have been extensively studied. Among them were derivatives of available drugs, but also alternative novel detergents such as Gemini surfactants. Over the last decade, they have been massively synthesized and studied to obtain the most effective antimicrobial agents, as well as the most selective aids for nanoparticles drug delivery. Various protocols and distinct bacterial strains used in Minimal Inhibitory Concentration experimental studies prevented performance benchmarking of different surfactant classes over these last years. Motivated by this limitation, we designed a theoretical methodology implemented in custom fast screening software to assess the surfactant activity on model lipid membranes. Experimentally based QSAR (quantitative structure-activity relationship) prediction delivered a set of parameters underlying the Diptool software engine for high-throughput agent-membrane interactions analysis. We validated our software by comparing score energy profiles with Gibbs free energy from the Adaptive Biasing Force approach on octenidine and chlorhexidine, popular antimicrobials. Results from Diptool can reflect the molecule behavior in the lipid membrane and correctly predict free energy of translocation much faster than classic molecular dynamics. This opens a new venue for searching novel classes of detergents with sharp biologic activity.