An understanding of how the amino acid sequence affects the interaction of peptides with lipid membranes remains mostly unknown. This type of knowledge is required to rationalize membrane-induced toxicity of amyloid peptides and to design peptides that can interact with lipid bilayers. Here, we perform a systematic study of how variations in the sequence of the amphipathic Ac-(FKFE)2-NH2 peptide affect its interaction with zwitterionic lipid bilayers using extensive all-atom molecular dynamics simulations in explicit solvent. Our results show that peptides with a net positive charge bind more frequently to the lipid bilayer than neutral or negatively charged sequences. Moreover, neutral amphipathic peptides made with the same numbers of phenylalanine (F), lysine (K), and glutamic (E) amino acids at different positions in the sequence differ significantly in their frequency of binding to the membrane. We find that peptides bind with a higher frequency to the membrane if their positive lysine side chains are more exposed to the solvent, which occurs if they are located at the extremity (as opposed to the middle) of the sequence. Non-polar residues play an important role in accounting for the adsorption of peptides onto the membrane. In particular, peptides made with less hydrophobic non-polar residues (e.g., valine and alanine) are significantly less adsorbed to the membrane compared to peptides made with phenylalanine. We also find that sequences where phenylalanine residues are located at the extremities of the peptide have a higher tendency to be adsorbed.
All Science Journal Classification (ASJC) codes
- Physical and Theoretical Chemistry
- Surfaces, Coatings and Films
- Materials Chemistry