Département de chimie moléculaire

How was created the very first dipeptides on earth, ca. 3.8 billion years ago That is the question we will address through a theor. study of the activation of methionine (Met) and N-formylmethionine (N-fMet) in aq. soln., and of their reactivity with alanine to form dipeptides.The direct condensation of two amino acids in aq. soln. is a thermodynamically disfavored process. Furthermore, without catalysis, it is so slow that it can be considered virtually impossible. It should not have occurred in the primitive ocean. But all the passed and present living is a magnificent proof that it has occurred ! A soln. to this paradox will be proposed.Today's, in eukaryotes and archaea, the first introduced amino acid in all peptides is Met. It is N-fMet in prokaryotes. We suggest that this choice was made at the very beginning of the history of life and propose activated forms of Met and N-fMet for the formation of the first dipeptides.This study uses ab initio dynamics performed in a periodic water box and the rare events issue is overcome by metadynamics. The proposed mechanism involved the formation of a hydroxyl ion and an explicit model of the solvent is indeed mandatory for a proper description of this crucial step. Then, we study the peptide bond formation vs. hydrolysis of the activated forms of Met and N-fMet. The results show that the formation of the dipeptide is much easier that the hydrolysis of the activated amino acid.