A density functional theory study of a concerted mechanism for proton exchange between amino acid side chains and water

A concerted mechanism for proton exchange between water and the amino acid side chains of cysteine, serine, arginine and glutamic acid has been investigated with hybrid density functional theory. The models used include, besides the amino acid side chain, a number of water molecules ranging from one to five in some cases. The modeling of the amino acids without their backbones is shown to be an excellent approximation. Long-range polarization effects were incorporated through a dielectric cavity method allowing a better comparison to existing measurements for free amino acids in water. The barriers converse rather fast with the number of water molecules for all the present amino acids and the converged values are in reasonable agreement with experiments with discrepancies in the range 2-6 kcal/mol. The dielectric effects were found to be small for all systems except cysteine, where there is a lowering of the barrier by 3-5 kcal/mol. The transition states for these concerted pathways form rings in which the separated charges can be stabilized.