QM/MM simulations as an assay for carbapenemase activity in class A β-lactamases

Ewa I Chudyk; Michael A L Limb; Charlotte Jones; James Spencer; Marc W van der Kamp; Adrian J Mulholland

doi:10.1039/c4cc06495j

QM/MM simulations as an assay for carbapenemase activity in class A β-lactamases

Ewa I Chudyk, Michael A L Limb, Charlotte Jones, James Spencer, Marc W van der Kamp, Adrian J Mulholland

Research output: Contribution to journal › Article (Academic Journal) › peer-review

43 Citations (Scopus)

376 Downloads (Pure)

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.

Original language	English
Pages (from-to)	14736-14739
Number of pages	4
Journal	Chemical Communications
Volume	50
Issue number	94
Early online date	2 Oct 2014
DOIs	https://doi.org/10.1039/c4cc06495j
Publication status	Published - 7 Dec 2014

Research Groups and Themes

Bristol BioDesign Institute
Physical & Theoretical

Keywords

synthetic biology
Enzyme Assays
Carbapenems
Bacterial Proteins
Hydrolysis
Quantum Theory
beta-Lactamases
Molecular Dynamics Simulation
Thermodynamics

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10.1039/c4cc06495j

c4cc06495jFinal published version, 2.09 MBLicence: CC BY

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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.",

keywords = "synthetic biology, Enzyme Assays, Carbapenems, Bacterial Proteins, Hydrolysis, Quantum Theory, beta-Lactamases, Molecular Dynamics Simulation, Thermodynamics",

author = "Chudyk, \{Ewa I\} and Limb, \{Michael A L\} and Charlotte Jones and James Spencer and \{van der Kamp\}, \{Marc W\} and Mulholland, \{Adrian J\}",

year = "2014",

month = dec,

day = "7",

doi = "10.1039/c4cc06495j",

language = "English",

volume = "50",

pages = "14736--14739",

journal = "Chemical Communications",

issn = "1359-7345",

publisher = "Royal Society of Chemistry",

number = "94",

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TY - JOUR

T1 - QM/MM simulations as an assay for carbapenemase activity in class A β-lactamases

AU - Chudyk, Ewa I

AU - Limb, Michael A L

AU - Jones, Charlotte

AU - Spencer, James

AU - van der Kamp, Marc W

AU - Mulholland, Adrian J

PY - 2014/12/7

Y1 - 2014/12/7

N2 - 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.

AB - 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.

KW - synthetic biology

KW - Enzyme Assays

KW - Carbapenems

KW - Bacterial Proteins

KW - Hydrolysis

KW - Quantum Theory

KW - beta-Lactamases

KW - Molecular Dynamics Simulation

KW - Thermodynamics

UR - https://www.scopus.com/pages/publications/84908638723

U2 - 10.1039/c4cc06495j

DO - 10.1039/c4cc06495j

M3 - Article (Academic Journal)

C2 - 25321894

SN - 1359-7345

VL - 50

SP - 14736

EP - 14739

JO - Chemical Communications

JF - Chemical Communications

IS - 94

ER -

QM/MM simulations as an assay for carbapenemase activity in class A β-lactamases

Abstract

Research Groups and Themes

Keywords

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Computational tools for enzyme engineering: bridging the gap between enzymologists and expert simulation

CCP-BioSim: Biomolecular simulation at the life sciences interface

COMPUTATIONAL BIOCHEMISTRY: PREDICTIVE MODELLING FOR BIOLOGY AND MEDICINE

HPC (High Performance Computing) and HTC (High Throughput Computing) Facilities

Professor Adrian J Mulholland

Dr Marc W Van der Kamp

Cite this

QM/MM simulations as an assay for carbapenemase activity in class A β-lactamases

Abstract

Research Groups and Themes

Keywords

Access to Document

Handle.net

Other files and links

Fingerprint

Projects

Computational tools for enzyme engineering: bridging the gap between enzymologists and expert simulation

CCP-BioSim: Biomolecular simulation at the life sciences interface

COMPUTATIONAL BIOCHEMISTRY: PREDICTIVE MODELLING FOR BIOLOGY AND MEDICINE

Equipment

HPC (High Performance Computing) and HTC (High Throughput Computing) Facilities

Profiles

Professor Adrian J Mulholland

Dr Marc W Van der Kamp

Cite this