An Efficient Computational Assay for β-Lactam Antibiotic Breakdown by Class A β-Lactamases

Viivi Hirvonen, Katharine Hammond, Ewa Chudyk, Michael Limb, James Spencer, Adrian Mulholland, Marc Van der Kamp

Research output: Contribution to journalArticle (Academic Journal)

4 Citations (Scopus)
14 Downloads (Pure)

Abstract

Class A β-lactamases cause clinically relevant resistance to β-lactam antibiotics. Carbapenem degradation is a particular concern. We present an efficient QM/MM molecular simulation protocol that accurately predicts the activity of β-lactamases against carbapenems. Simulations take less than 24 CPU hours, a greater than 99% reduction, and do not require fitting against experimental data or significant parametrization. This computational assay also reveals mechanistic details of β-lactam breakdown and should assist in evaluating emerging β-lactamase variants and developing new antibiotics.
Original languageEnglish
Pages (from-to)3365-3369
Number of pages5
JournalJournal of Chemical Information and Modeling
Volume59
Issue number8
Early online date30 Jul 2019
DOIs
Publication statusE-pub ahead of print - 30 Jul 2019

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