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 alpha-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 alpha-helix structure. Here, we perform molecular dynamics simulations to study the hydration of polyALA, polyserine (polySER) and other homopolymer peptide alpha-helices at different temperatures and pressures. We find that water molecules form HB with most polyALA carbonyl O atoms, despite ALA hydrophobic CH3CH3 side chain. Similar water-peptide backbone HB are found in other (hydrophobic and hydrophilic) homopolymer alpha-helices with large side chains, including polyvaline, polyleucine and polyphenylalanine. A novel hydration mechanism is observed in 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 theta(c) of a water droplet pierced by a long polyALA/polySER alpha-helix. Unexpectedly, even when polyALA alpha-helix is supposed to be hydrophobic (theta(c)>900), we find that theta(c)approximate to 790. For polySER, theta(c)approximate to 700, consistent with alpha-helical polySER being hydrophilic.