Charge Ratio and Distribution Effects on Lys/Ala Peptide Conformation and Adsorption onto the Lipid Bilayer Membrane (POPS)

In the present work, molecular dynamics simulations were performed to investigate peptide samples composed of lysine (Lys) and alanine (Ala) residues interacting with an anionic lipid bilayer membrane. We systematically examined how the sequence pattern, lysine content, and charge distribution along the peptide chain govern the structural properties and their adsorption onto the 1-palmitoyl-2-oleoyl-sn-glycero-3-phospho-L-serine (POPS) membrane. Our results reveal that both the radius of gyration (Rg) and the root-mean-square deviation (RMSD) increase with chain length, reflecting greater conformational entropy in longer chains. The scaling exponent ν derived from the power-law analysis of Rg indicates that the peptide chains adopt highly extended conformations. Notably, ν decreases with increasing lysine ratio of the peptide chain, which can be rationalized by the competition between intrachain electrostatic repulsion and membrane-induced electrostatic anchoring. Root-mean-square fluctuation (RMSF) analysis reveals a characteristic double-well profile, with overall flexibility increasing with chain length, and lysine residues consistently exhibit higher local flexibility than alanine. Simulation results also show that peptides with the same charge ratio but different spatial distributions exhibit distinct conformational dynamics and membrane adsorption behavior, demonstrating that the spatial distribution of charged Lys residues, rather than chain length or net charge, governs peptide–membrane contacts and adsorption kinetics. Increasing the Lys fraction strengthens electrostatic anchoring, promotes peptide extension along the membrane plane, and restricts motion normal to the membrane, resulting in pronounced conformational anisotropy. In terms of adsorption, the all-Ala peptide cannot adsorb stably, whereas Lys-containing peptides adsorb stably onto the POPS membrane, with faster adsorption at higher Lys content up to 75%. These findings may provide clear design principles for tuning peptide conformation and membrane adsorption by controlling charge ratio and spatial distribution, and ultimately offer a practical possibility for their application in biotechnology.