Small molecule interaction with lipid bilayers: a molecular dynamics study of chlorhexidine.
Chlorhexidine (CHX) is an effective anti-bacterial agent whose mode of action is thought to be the disruption of the cell membrane. We tested the capability of the Slipids all atom force fields using data from neutron scattering and NMR experiments on the drug chlorhexidine in a 1,2-dimyrisoyl-3-sn-phosphatidylcholine (DMPC) membrane. Since it is not known what the charge of the CHX molecule is inside an apolar environment, a neutral, as well as a +1 and +2 charge model for the molecule were created and tested at several concentrations. This study shows that the location of CHX is minorly dependent on concentration, and dominantly reliant on the charge. The effect of adding CHX to DMPC is a thinning of the membrane, thus increasing the area per lipid.
Physics Department, Brock University, St. Catharines, Ontario L2S 3S1, Canada. Electronic address: bv07ay@brocku.ca.
Brad
B
Van Oosten
Physics Department, Brock University, St. Catharines, Ontario L2S 3S1, Canada.
Drew
D
Marquardt
Physics Department, University of Guelph, Guelph, Ontario N1G 2W1, Canada.
Ivana
I
Komljenović
College of Medicine and Veterinary Medicine, The University of Edinburgh, Edinburgh EH16 4SB, UK.
Jeremy P
JP
Bradshaw
Physics Department, Brock University, St. Catharines, Ontario L2S 3S1, Canada.
Edward
E
Sternin
Physics Department, Brock University, St. Catharines, Ontario L2S 3S1, Canada.
Thad A
TA
Harroun
D000900:Anti-Bacterial Agents / Q000737:chemistry*; D002710:Chlorhexidine / Q000737:chemistry*; D004134:Dimyristoylphosphatidylcholine / Q000737:chemistry; D006860:Hydrogen Bonding; D008051:Lipid Bilayers / Q000737:chemistry*; D062105:Molecular Docking Simulation; D033363:Neutron Diffraction
D000900:Anti-Bacterial Agents; D008051:Lipid Bilayers; D002710:Chlorhexidine; D004134:Dimyristoylphosphatidylcholine
Chlorhexidine; DMPC; GROMACS; NMR; Neutron diffraction; Slipids