Projects per year
Clavulanate is used as an effective drug in combina-tion with β-lactam antibiotics to treat infections of some antibiotic resistant bacteria. Here, we per-form combined quantum mechanics / molecular mechanics simulations of several covalent com-plexes of clavulanate with class A β-lactamases KPC-2 and TEM-1. Simulations of the deacylation reactions identify the decarboxylated trans-enamine complex as responsible for inhibition. Further, the simulations correctly discriminate between enzymes that are effectively inhibited (TEM-1) from those that are not (KPC-2) providing a 'computational assay' for clinically relevant inhibition.
Multi-scale enzyme modelling for SynBio: optimizing biocatalysts for selective synthesis of bioactive compounds
1/12/15 → 30/11/20