Understanding the Helical Stability of Charged Peptides

α-helices play an essential role in the tertiary and quaternary folding of a protein and are vital for protein functioning. Helical peptides have found their applications in membrane transport, vaccine development, and therapeutics. Their application is limited because of the reduced solubility of the hydrophobic residue helices and the low stability of the helices with charged amino acids in the aqueous solution. This study aims to bridge this gap by designing water-soluble helical peptides by controlling the charge density and the amino acid sequence. In this study, we used leucine (hydrophobic) and lysine (charged) amino acid residues to design proteins with considerably higher stability than fully charged polypeptides. Results from Molecular Dynamics Simulations show that charge density plays a central role in tuning the helical stability. At a fixed charge density, the sequence pattern has a minor influence. We believe this study could help the scientific community involved in the de novo design of protein sequences.