Deciphering the Impact of Cyclization and Lysine Charges on Antimicrobial Peptides Using Molecular Dynamics Simulations and Density Functional Theory

Abstract

AbstractThis study utilized molecular dynamics simulations (MD) to explore the impact of cyclization and lysine charges on antimicrobial peptides (AMPs) across eight simulation boxes designed with water and water‐sodium dodecyl sulfate (SDS) micelles. Cyclic AMPs with positively charged lysine residues (c‐AMP+) displayed increased stability in both environments compared to linear AMPs (l‐AMP+), with removal of positive charges notably destabilizing the linear form in water‐SDS. Findings revealed enhanced mobility due to cyclization and charged lysine residues, further boosted by SDS presence. Notably, lysine residues exhibited a stronger affinity for SDS than tryptophan and phenylalanine, especially lysine number 5. Analysis extended to peptide backbone conformation and electronic features, showing cyclization's greater impact on psi and phi angles over charge presence, with linear AMPs displaying lower reactivity than cyclic counterparts. This research underscores the significance of cyclization and lysine charges in AMP behavior, suggesting the potential of c‐AMP+ for further development owing to their improved stability, mobility, and membrane interactions.