Unraveling the role of counter ions in shaping the structures of helical peptides in aqueous phase

Abstract Helical peptides, as well as proteins composed of helical peptides, play essential roles in various biological processes, including their functions as components of cell membranes and their interactions with biological membranes. Therefore, it is crucial to predict the propensity and structural characteristics of helices formed in solution or lipid environments for specific peptide sequences. Melittin and pexiganan are antimicrobial peptides (AMPs) that possess distinct sequence characteristics but exhibit similar structural properties in both solution and lipid environments. In this study, we conducted molecular dynamics simulations to investigate how the presence of counter ions creates differences in structural characteristics between these two peptides in solution. By analyzing the structures formed for each AMP using extended helical projections, we aimed to uncover the underlying principles governing the interaction between counter ions and peptide sequences, leading to the formation of stable structures. It was found that the coordination of counter ions effectively extends the helical surface and stabilizes the extended helix by reducing the electrostatic repulsion between charged residues. Our results demonstrate how sequence specificity influences helical structure formation in solution and provide an explanation for the varying degrees of synergistic effects exhibited by different helical AMPs.