A Systematic Approach: Molecular Dynamics Study and Parametrisation of Gemini Type Cationic Surfactants.

Mateusz Rzycki,Dominik Drabik,Aleksandra Kaczorowska,Sebastian Kraszewski

doi:10.3390/ijms222010939

Abstract

The spreading of antibiotic-resistant bacteria strains is one of the most serious problem in medicine to struggle nowadays. This triggered the development of alternative antimicrobial agents in recent years. One of such group is Gemini surfactants which are massively synthesised in various structural configurations to obtain the most effective antibacterial properties. Unfortunately, the comparison of antimicrobial effectiveness among different types of Gemini agents is unfeasible since various protocols for the determination of Minimum Inhibitory Concentration are used. In this work, we proposed alternative, computational, approach for such comparison. We designed a comprehensive database of 250 Gemini surfactants. Description of structure parameters, for instance spacer type and length, are included in the database. We parametrised modelled molecules to obtain force fields for the entire Gemini database. This was used to conduct in silico studies using the molecular dynamics to investigate the incorporation of these agents into model E. coli inner membrane system. We evaluated the effect of Gemini surfactants on structural, stress and mechanical parameters of the membrane after the agent incorporation. This enabled us to select four most likely membrane properties that could correspond to Gemini’s antimicrobial effect. Based on our results we selected several types of Gemini spacers which could demonstrate a particularly strong effect on the bacterial membranes.

Highlights

Antimicrobial resistance against available antibiotics has been acknowledged as one of the most serious problems in medicine nowadays
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
We included those parametrised force fields in Supporting Materials (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

Summary

Introduction

Antimicrobial resistance against available antibiotics has been acknowledged as one of the most serious problems in medicine nowadays This resulted in a surge of new research works related to the synthesis of novel compounds that could serve as a potential modern-generation groups of antimicrobial particles. One of these groups are Gemini surfactants (initially referred to as bis-surfactants), which are heavily reported for their antimicrobial effect [1]. They consist of two amphiphilic groups connected by a spacer at the head level, which can be both hydrophilic and hydrophobic [2,3]. They have at least two hydrophobic chains and two ionic or polar groups

Methods

Results

Conclusion