Our results show that the inhibition process with the two compounds takes place by a two-step mechanism, in which the formation of a high energy intermediate (the C145 - /H41 + ion pair) precedes the protein-inhibitor covalent bond formation. Analysis of the free energy profiles, the geometries of the states appearing along the reaction path, as well as the interactions established between the inhibitors and the different pockets of the active site on the protein confirms a measurable impact of the warhead in the kinetics and thermodynamics of the process of the second step.