Garcia-Borràs, Marc

Enzymatic reactive intermediates are species involved in biocatalytic cycles that are not so stable and exhibit short lifetimes. Catalytic promiscuity refers to the ability of an enzyme to catalyze, in addition to its native function, reactions involving different substrates and/or that proceed via different transition states and different reaction pathways. Enzymatic intermediates are sometimes found to be the source of enzyme catalytic promiscuity, since different reaction pathways can diverge from these generated species. Consequently, controlling the behavior of such reactive species could provide new routes to access to new non-natural biocatalytic functions.
In this research program new computational protocols to study and characterize reactive intermediates formed over the course of enzyme catalytic pathways will be developed. These protocols will rely on different multiscale computational approaches that will be combined to account for different factors that play key roles on the formation and stabilization of enzymatic reactive intermediates and that control their subsequent reactivity. State-of-the-art computational techniques including DFT calculations, Molecular Dynamics (MD) simulations, QM/MM calculations, and direct quasi-classical reaction dynamics MD simulations, among others, will be part of such protocols. In particular, enzymatic systems involving metalloenzymatic and photobiocatalytic intermediates will be targeted.
Also, molecular biology experiments and structural chemical characterization of the biocatalytic products will be performed in order to assess the computational predictions and designs, providing further guidance for computational modelling.
Finally, the knowledge acquired will be used to computationally design new enzymes for catalyzing new-to-nature reactions interesting for synthetic purposes in a more rational and efficient manner.