Stabilization of zwitterionic versus canonical proline by water molecules.

At physiological conditions, a majority of biomolecules (e.g., amino acids, peptides and proteins) exist predominantly in the zwitterionic form that usually decides the biological functions. However, zwitterionic amino acids are not geometrically stable in gas phase and this seriously hampers the understanding of their structures, properties and biological functions. To this end, one of the recent research focuses is to demonstrate the stabilization effects of zwitterionic amino acids. Relative stabilities of canonical conformers are dependent on water contents, while zwitterionic stability improves monotonously and pronouncedly with increase of water contents. We find that one water molecule can render zwitterionic proline geometrically stable, and stabilities of different zwitterionic amino acids increase as glycine <proline <arginine. In addition, we have determined the numbers of water molecules required for zwitterionic proline to be energetically preferential and conformationally predominant, respectively as four and five. Five water molecules are enough to fill up the first shell of proline functional sites (carboxylic and amido), which is in line with the results of glycine. At any water content, zwitterionic formation will not be hindered kinetically because of rather low activation barriers, and the distribution of zwitterionic amino acids will be largely dependent on their thermodynamic stabilities.