The water molecule arrangement over the side chain of some aliphatic amino acids: A quantum chemical and bottom-up investigation

The geometry of surrounding water molecules on the side chain of glycine, alanine, α-aminoisobutyric acid, α-aminobutyric acid, valine, and related hydrocarbons has been analyzed combining bottom-up and quantum chemical methodologies. To minimize the cavity size and to prevent water-water hydrogen bonding loss, the water molecules adopt a shape, resembling the one found in crystal structure of gas clathrate hydrates, with water molecules tangentially oriented to the surface of hydrophobic side chain. The cage is directly hydrogen bonded to the backbone's polar groups, thus hydration shells around hydrophobic and hydrophilic groups are folded together in amphiphilic molecules. The hydrophobe enclathration implies a substantial freedom degree reduction which makes it entropically disfavored. This disadvantageous entropic contribution is partially compensated by the favorable van der Waals interactions with guest in stabilizing clathrate hydrate formation. The water shell around the side chain relates intimately with the side-chain rotational isomerism. Present data are correlated with the experimental determined populations of the three rotamers, yielding promising results for both α-aminobutyric acid and valine.