Modeling peptide-membrane interactions
Proteins, 58:518-27 (2005)
The peptide K3F2 bound to anionic (left) or zwitterionic (right) membrane
The IMM1 implicit membrane model was supplemented with a
Gouy-Chapman term describing counterion-screened electrostatic interactions of
a solute with negatively charged membrane lipids. The new model was tested on
peptides that bind to anionic membranes. Pentalysine binds just outside the
plane of negative charge whereas Lys-Phe peptides insert their aromatic rings
into the hydrophobic core. Melittin and magainin 2 bind more strongly to
anionic than to neutral membranes and in both cases insert their hydrophobic
residues into the hydrocarbon core. The third domain of Antennapedia homeodomain
(penetratin) binds as an a-helix in the headgroup region. Cardiotoxin II binds strongly to anionic membranes but marginally to neutral ones.
In all cases, the location and configuration of the peptides are consistent
with experimental data and the effective energy changes upon binding compare
favorably with experimental binding free energies. The model opens the way to
exploring the effect of membrane charge on the location, conformation, and
dynamics of a large variety of biologically active peptides on membranes.