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.
|Number of pages||4|
|Early online date||29 May 2018|
|Publication status||E-pub ahead of print - 29 May 2018|
FingerprintDive into the research topics of 'Multiscale simulations of clavulanate inhibition identify the reactive complex in class A β-lactamases and predict efficiency of inhibition'. Together they form a unique fingerprint.
- 3 Finished
Link account to CHEM RB1768 (EP/M027546/1) - Bristolbridge-Nanospears
11/01/16 → 10/04/16
Multi-scale enzyme modelling for SynBio: optimizing biocatalysts for selective synthesis of bioactive compounds
1/12/15 → 31/05/21
CCP-BioSim: Biomolecular Simulation at the Life Sciences Interface
1/07/15 → 30/04/21