title: QM/MM simulations as an assay for carbapenemase activity in class A β-lactamases.
abstract: Carbapenems, 'last resort' antibiotics for many bacterial infections, can now be broken down by several class A β-lactamases (i.e. carbapenemases). Here, carbapenemase activity is predicted through QM/MM dynamics simulations of acyl-enzyme deacylation, requiring only the 3D structure of the apo-enzyme. This may assist in anticipating resistance and future antibiotic design.
authors.affiliation: Centre for Computational Chemistry, School of Chemistry, University of Bristol, Cantock's Close, Bristol, BS8 1TS, UK. marc.vanderkamp@bristol.ac.uk adrian.mulholland@bristol.ac.uk.
authors.forename: Ewa I
authors.initials: EI
authors.lastname: Chudyk
authors.forename: Michael A L
authors.initials: MA
authors.lastname: Limb
authors.forename: Charlotte
authors.initials: C
authors.lastname: Jones
authors.forename: James
authors.initials: J
authors.lastname: Spencer
authors.forename: Marc W
authors.initials: MW
authors.lastname: van der Kamp
authors.forename: Adrian J
authors.initials: AJ
authors.lastname: Mulholland
mesh_terms: D001426:Bacterial Proteins / Q000737:chemistry / Q000378:metabolism*; D015780:Carbapenems / Q000378:metabolism; D057075:Enzyme Assays; D006868:Hydrolysis; D056004:Molecular Dynamics Simulation; D011789:Quantum Theory; D013816:Thermodynamics; D001618:beta-Lactamases / Q000737:chemistry / Q000378:metabolism*
chemical_list: D001426:Bacterial Proteins; D015780:Carbapenems; D001618:beta-Lactamases; C063912:carbapenemase