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. 2021 Oct 27;14(21):6455.
doi: 10.3390/ma14216455.

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

Mateusz Rzycki  1   2 , Sebastian Kraszewski  2 , Marta Gładysiewicz-Kudrawiec  1
Affiliations

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

Mateusz Rzycki et al. Materials (Basel). .

Abstract

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.

Keywords: drug delivery; free energy calculation; lipid membranes; molecular dynamics; numerical tool; surfactants.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
The chemical structures of antibacterial agents (A) OCT and (B) CHX.
Figure 2
Figure 2
Initial and final trajectories obtained from (A) ABF−method, (B) Diptool software on PG membranes. CHX: green sticks and surface, OCT: violet sticks and surface, POPG: blue and pink sticks, phosphorous atoms: cyan beads, nitrogen atoms: orange beads and PG membrane dipoles: teal beads.
Figure 3
Figure 3
The comparison between MD−ABF and Diptool free energy calculation, marked in black and red, respectively. (A) Free energy transfer for OCT in PC membrane, (B) Free energy transfer for OCT in PG membrane, (C) Free energy transfer for CHX in PC membrane, (D) Free energy transfer for CHX in PG membrane.
See this image and copyright information in PMC

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