Water catalyzed peptide bond formation in l-alanine dipeptide: The role of weak hydrogen bonding

Abstract

This paper reports the study on the catalytic effect of a single water molecule on the peptide bond formation in l-alanine dipeptide using ab-initio methods at the HF/6-31G ∗ level of theory and comparison with the corresponding noncatalyzed reaction. Both concerted and stepwise mechanisms are studied. Zero point corrections are made and thermodynamic parameters are evaluated. The barrier heights are systematically lowered in the water-catalyzed reaction compared to the noncatalyzed reaction. It is further observed that the barrier heights of the transition states relative to the reactant for the noncatalyzed and water-catalyzed reactions are different due to hydrogen bonding of the reactant alanine molecules with the ancillary water molecule in the later case. While the C N bond formation preceded by a proton transfer is the rate determining step in the noncatalyzed reaction rather than the following step in which the leaving group departures followed by a proton transfer, the two steps are competitive with each other in the water-catalyzed reaction. This is due to the similarity in geometry and partial charges of the two transition states in their overall hydrogen-bonded structure. Effect of electron correlation is calculated at the MP2/6-31G ∗ level using the optimized geometry obtained at the HF/6-31G ∗ level of theory which does not change the relative heights of the transition states. However, inclusion of the electron correlation lowers the energy of the product states in both cases and the reactions become slightly exothermic. The present study draws the attention to the possible catalyzing role of water in the peptide bond formation.