Small molecule interaction with lipid bilayers: a molecular dynamics study of chlorhexidine

Area of Science:

• Computational Biophysics
• Membrane Biophysics
• Pharmacology

Background:

• Chlorhexidine (CHX) is a widely used antibacterial agent.
• Its mechanism of action is believed to involve disruption of bacterial cell membranes.
• Understanding CHX-membrane interactions is crucial for its effective application.

Purpose of the Study:

• To evaluate the accuracy of Slipids all-atom force fields for simulating CHX in lipid membranes.
• To investigate the influence of CHX charge state and concentration on its location within a DMPC membrane.
• To determine the effect of CHX on DMPC membrane structure.

Main Methods:

• Utilized neutron scattering and NMR experimental data.
• Employed all-atom molecular dynamics simulations with Slipids force fields.
• Tested neutral, +1, and +2 charged models of CHX at various concentrations within a 1,2-dimyristoyl-3-sn-phosphatidylcholine (DMPC) membrane.

Main Results:

• CHX location within the DMPC membrane is predominantly determined by its charge state.
• Membrane location shows minimal dependence on CHX concentration.
• Addition of CHX leads to membrane thinning and an increase in the area per lipid.

Conclusions:

• The Slipids force field, validated by experimental data, accurately models CHX-membrane interactions.
• The charge of the chlorhexidine molecule significantly dictates its interaction and location within lipid bilayers.
• CHX alters membrane structure by thinning it, which has implications for membrane function and drug efficacy.