**4. Conclusions**

In this work, we optimised and parametrised 250 Gemini molecules. We described each of those molecules with theoretical values of logP and log (CMC) as well as provided a detailed description of those molecules in the attached spreadsheet. Additionally, we included those parametrised force fields in SM for future simulation studies. This may be remarkably helpful in further antimicrobial action studies, as a significant number of Gemini cationic molecules with various spacers were modelled and parametrised. Such systematic summarisation may be extensively used not only for theoretical studies but also for experimental ones with the aim to deliver comprehensive knowledge and molecular mechanism of surfactant effectiveness. Furthermore, we selected 25 molecules from various groups and simulated their behaviour in systems with membrane mimicking the inner membrane of *E. coli*. This detailed characterisation of parameters allowed us to extract four types of parameters—area compressibility, bending rigidity, lateral diffusion coefficient and membrane surface tension—that could correspond to the antimicrobial

effect of those molecules. Based on our preliminary screening we concluded that the type of Gemini molecules that could exhibit strong antimicrobial effects are oQAS, Pyr, Imo. Additionally, other possible candidates are Ary, Glu, hQAS and Alk. In this work we proposed and deliver a uniform theoretical approach to compare Gemini surfactant effectiveness. Nevertheless, this systematic approach should be confirmed experimentally to provide solid biological relevance.

**Supplementary Materials:** The following are available online at https://www.mdpi.com/article/10 .3390/ijms222010939/s1: (1) Gemini molecules database (.xls). (2) Complete force-fields for Gemini molecules from the database (.zip). (3) Supporting materials (.docx) including system density profiles of investigated agents, table with membrane system characterisation and instruction for NAMD FF to GROMACS FF conversion.

**Author Contributions:** Conceptualisation, M.R. and D.D.; methodology, M.R., A.K. and D.D.; validation, M.R. and D.D.; formal analysis, M.R. and D.D.; investigation, M.R., A.K. and D.D.; resources, S.K.; data curation, M.R., A.K. and D.D.; writing—original draft preparation, M.R. and D.D.; writing— review and editing, M.R., A.K. and D.D.; visualisation, M.R. and D.D.; supervision, D.D.; project administration, S.K.; funding acquisition, S.K. All authors have read and agreed to the published version of the manuscript.

**Funding:** This work was possible thanks to the financial support from the National Science Centre (Poland) gran<sup>t</sup> No. 2015/19/B/NZ7/02380. Additionally, D.D. acknowledge support from National Science Center (grant number 2018/30/E/NZ1/00099).

**Data Availability Statement:** Most of the data are available in the manuscript supplementary information, including force fields. The simulation data presented in this study are available on request from the corresponding author due to GBs files sizes.

**Acknowledgments:** We would like to thank both Kamila Szostak-Paluch and Beata Hanus-Lorenz from Wroclaw University of Science and Technology for valuable discussion regarding structures of cationic Gemini molecules.

**Conflicts of Interest:** The authors declare no conflict of interest.
