Determining Structure and Action Mechanism of Artificial Peptide LBF14 by Molecular Simulation

Membrane-active peptides (MAP) interact with biomembranes though binding, deformation, penetration or disruption of membranes, or transport of other molecules through a membrane. Some MAPs are used as an antimicrobial defense mechanism by many organisms. Others may be used to transport drugs across a cell membrane into the target cell. Recently a new membrane-active peptide called LBF14 which contains non-proteinogenic amino acids was discovered.

We analyze the structure of this peptide in free solution and bound to a lipid membrane. We also study the influence of protonation of His residues and determine the impact of a bound peptide on membrane structure. The simulations suggest that the peptide consists of a small helical section in an otherwise random structure. Histidine protonation appears to impact the stability of the helix, an effect that can potentially be explained by the electrostatic repulsion with the neighboring amino acid Ornithine. The secondary structure of the peptide did not change upon membrane interaction. However, a change in backbone dihedral angles allows two hydrophobic residues to immerse deeper into the membrane.