Molecular dynamics simulations to study the role of biphenylalanine in promoting the antibacterial activity of ultrashort peptides

Abstract

The hydrophobic amino acid biphenylalanine (B) plays a key role in the antibacterial activity of ultrashort peptides. In this study, the interactions of tetrapeptide BRBR-NH2 (BRBR) and pentapeptide BRBRB-NH2 (BRBRB) with dioleoylphosphatidylcholine/dioleoylphosphatidylglycerol (DOPC/DOPG) mixed model membrane were studied by molecular dynamics simulation to assess the role of biphenylalanine in promoting the antibacterial activity of ultrashort peptides. At low peptide concentrations, both peptides presented amphiphilic conformations; residues B of the pentapeptide approached the membrane faster than those of the tetrapeptide and made more contacts with the membrane; BRBRB exhibited stronger membrane affinity than BRBR. However, due to the low peptide concentrations, the effects of these two peptides on the membrane were not significantly different. At high peptide concentrations, the strong affinity of BRBRB made it have more interaction with membrane than BRBR and most residues B of BRBRB inserted into the membrane; BRBRB was more prone to aggregation and caused the membrane more disordered and thinner than BRBR. Hydrophobic residues often act as anchors in the antibacterial activity of ultrashort antimicrobial peptides. Adding a hydrophobic residue B to the C-terminal of BRBR could improve the ability of the peptide to “grasp” the membrane. At high peptide concentrations, the addition of residue B might enhance the antibacterial activity of the peptide. Thus, our results will be helpful in designing efficient antibacterial drugs.