(511f) Solvation Contribution to the Conformational Preferences of the Hydrated Peptides

Previous studies have shown that disordered polar peptides such as polyglycine prefer collapsed structures in an aqueous solution, suggesting that water is a poor solvent even for a protein backbone lacking hydrophobic sidechain residues. This raises several intriguing possibilities with regard to the role of water-mediated “hydrophobic” interactions in the behavior of solvated proteins. We use all-atom simulations, coupled with advanced sampling methods, of solvated model peptides to delineate various free energy contributions that govern their behavior. Our results highlight important role of favorable direct protein-water interactions in counterbalancing the unfavorable indirect cavity contribution in case of model peptides. Furthermore, the presence of secondary structures can favor the stabilization of peptide conformations that are not necessarily the most compact ones. Most importantly, our results are found to be largely insensitive to the variations in the protein and solvent force fields.