Backbone Hydration of -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 -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 -helix structure. Here, we perform molecular dynamics simulations to study the hydration of polyALA, polyserine (polySER), and other homopolymer peptide -helices at different temperatures and pressures. We find that water molecules form HB with most polyALA carbonyl O atoms, despite ALA hydrophobic CH side chain. Similar water-peptide backbone HB are found in other (hydrophobic and hydrophilic) homopolymer -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 of a water droplet pierced by a long polyALA/polySER -helix. Unexpectedly, even when polyALA -helix is supposed to be hydrophobic ( > 90°), we find that ≈ 79°. For polySER, ≈ 70°, consistent with -helical polySER being hydrophilic.