Backbone hydration of α -helical peptides: hydrogen-bonding and surface hydrophobicity/hydrophilicity

The stability of proteins and small peptides depends on the way they interact with the surrounding water molecules. For small peptides, such as α-helical polyalanine (polyALA), water molecules can weaken the intramolecular hydrogen-bonds (HB) formed between the peptide backbone O and NH groups which are responsible for the α-helix structure. Here, we perform molecular dynamics simulations to study the hydration of polyALA, polyserine (polySER), and other homopolymer peptide α-helices at different temperatures and pressures. We find that water molecules form HB with most polyALA carbonyl O atoms, despite ALA hydrophobic CH3 side chain. Similar water-peptide backbone HB are found in other (hydrophobic and hydrophilic) homopolymer α-helices with large side chains, including polyvaline, polyleucine, and polyphenyalanine. A novel hydration mechanism is observed in polyserine (polySER): the backbone peptide rarely forms HB with water and, instead, the carbonyl O atoms tend to form HB with polySER side chain OH groups. We also quantify the hydrophobicity/hydrophilicity of polyALA and polySER by calculating the contact angle θ c of a water droplet pierced by a long polyALA/polySER α-helix. Unexpectedly, even when polyALA α-helix is supposed to be hydrophobic (θ c > 90°), we find that θ c ≈ 79°. For polySER, θ c ≈ 70°, consistent with α-helical polySER being hydrophilic.