Influence of the Lipid Headgroup Composition on the Binding of the Antimicrobial Peptide BP100

Membrane active antimicrobial peptides are a promising class of drugs to manage
the fight against multi-resistant bacteria and fungi. One of factors that confer
selectivity towards pathogens is the difference in negative charge density of
mammalian and bacterial membranes. However, different bacterial species have
very different lipid compositions. Headgroups affect properties such as melting point,
solubility, packing and curvature preferences of lipid aggregates.
Phosphatidylcholine (PC) lipids are more abundant in mammalians and
phosphatidylethanolamine (PE) is more common in bacteria. However there are
bacteria and fungi that present both.
PE presents a higher tendency for negative curvature and a higher number of
hydrogen bonds in an aggregate. To give an idea of the differences between PC and
PE, the melting point of palmitoyloleoylphosphatidylcholine is around -2 o C while the
melting point of palmitoyloleoylphosphatidylethanolamine is around 25 o C. The
difference in the properties of PC and PE can potentially also have an impact the
interaction between drug and target, leading to varying efficiencies. As such, detailed
biophysical analysis of the influence of lipid headgroups in the antimicrobial peptide
activity may provide an opportunity for further targeted structure based drug design.
We are undertaking computational studies of the interaction between BP100 (H-
KKLFKKILKYL-NH2) a short, cationic, alpha helical peptide and membranes of
different compositions, both in charge and headgroups. The simulations set up is a
single peptide placed among water molecules and a lipid membrane in the middle of
the simulation box, properly hydrated and with the appropriate counterions. The
forcefields of choice are the Charmm36 and Charmm36m.
This work was supported by Conselho Nac. Des. Cient. Tecnologico (CNPq) and by
the Laboratório Nacional de Computação Científica (LNCC)