I see my role in this COST Action in applying diverse computational approaches to model the various kinetic and thermodynamic aspects of the biological systems that are in the focus of the Action. This will help in revealing the precise molecular mechanism and the related free-energy profiles of the catalytic activity and inhibition of several enzymes, thus aid in interpreting multidisciplinary biochemical research proposed here and provide directions for the design of the efficient inhibitors as transition-state analogues. Computational simulations will be used to identify the key residues responsible for the inhibitor binding and complex/adduct stabilization, thus guiding in the selection of point mutations for experimental studies and the cell biology investigations. Having the input from the isotope labeling experiments, we shall apply advanced nuclear quantization simulations to model the kinetic isotope effects that would provide further support to the proposed mechanisms in both wild-type and mutant enzymes. After the initial set of theoretical results, the subsequent experimental data will further refine our models in an iterative manner.