Influence of the membrane dipole potential on peptide binding to lipid bilayers

Abstract

The implicit membrane model IMM1 is extended to include the membrane dipole potential and applied to molecular dynamics simulations of the helical peptides alamethicin, WALP23, influenza hemagglutinin fusion peptide, HIV fusion peptide, magainin, and the pre-sequence of cytochrome c oxidase subunit IV (p25). The results show that the orientation of the peptides in the membrane can be influenced by the dipole potential. The binding affinity of all peptides except for the hemagglutinin fusion peptide decreases upon increase of the dipole potential. The changes in both orientation and binding affinity are explained by the interaction of the dipole potential with the helix backbone dipole and ionic side-chains. In general, peptides that tend to insert the N-terminus in the membrane and/or have positively charged side chains will lose binding affinity upon increase of the dipole potential.

Molecular dynamics simulations of biological membranes and membrane proteins using enhanced conformational sampling algorithms

“…Recently, the IMM1 model has been extended to model lipid bilayers with a transmembrane potential [126,127], with aqueous pores [128,129], with anionic lipids [130], and mixed lipid bilayers with lateral pressure effects [131]. The transmembrane potential can be considered by introducing the analytical solution of the PB equation [102] or by introducing an empirical monotonic function along the membrane normal [126,127].…”

“…The transmembrane potential can be considered by introducing the analytical solution of the PB equation [102] or by introducing an empirical monotonic function along the membrane normal [126,127]. This method makes it possible to study mechanisms of voltage-dependent insertion of peptide and channel gating in the implicit solvent.…”

Recent Results in Alamethicin Research

“…that the ALM peptides adopted a diverse set of conformations in the lipid bilayer. [60] performed MD simulations on ALM applying an implicit membrane model with membrane dipole potential in order to investigate the interactions between ALM and a zwitterionic bilayer. In the course of this theoretical study, the effects of membrane dipole potential produced on the orientation and the binding energy of peptides were determined.…”

Strategies for Exploring Electrostatic and Nonelectrostatic Contributions to the Interaction of Helical Antimicrobial Peptides with Model Membranes

“…Notwithstanding these results, the fluorophores (tryptophan in Ac-L1A and Abz in Abz-L1A-V8W) were more screened to the quencher acrylamide, in both zwitterionic and anionic vesicles, indicating that the modifications favored higher perturbation of the lipid packing. This is probably due to the decrease of the repulsive interaction between lipid dipoles and N-terminus charge [129].…”