Molecular dynamics study of the internalization of cell-penetrating peptides containing unnatural amino acids across membranes

(KAibG), that previously showed high cell internalization efficiency. KAibA and KAibG displayed the lowest internalization energies among the studied CPPs, showing distinct internalization mechanisms depending on the lipid composition of the model membranes. The presence of Aib residues allows these CPPs to adopt amphipathic folding to efficiently penetrate through the membranes. Elucidating how Aib incorporation affects CPP-membrane binding and interactions is beneficial for the design of CPPs for efficient intracellular delivery.