Efflux pump-mediated antibiotics resistance: Insights from computational structural biology

• Published in: Interdisciplinary sciences : computational life sciences 2014-03, Vol.6 (1), p.1-12
• Main Authors: Fischer, Nadine, Raunest, Martin, Schmidt, Thomas H., Koch, Dennis C., Kandt, Christian
• Format: Article
• Language: English
• Subjects: Antibiotics; Bacterial Outer Membrane Proteins - metabolism; Biomedical and Life Sciences; Computational Biology/Bioinformatics; Computational Science and Engineering; Computer Appl. in Life Sciences; Computer Simulation; Drug Resistance, Multiple, Bacterial; E coli; Energy conversion; Escherichia coli - drug effects; Escherichia coli - metabolism; Escherichia coli Proteins - metabolism; Health Sciences; Life Sciences; Mathematical and Computational Physics; Medicine; Membrane Transport Proteins - metabolism; Molecular Conformation; Molecular Dynamics Simulation; Protons; Pseudomonas aeruginosa - drug effects; Pseudomonas aeruginosa - metabolism; Pumps; Software; Statistics for Life Sciences; Theoretical; Theoretical and Computational Chemistry
• ISSN: 1913-2751; 1867-1462
• DOI: 10.1007/s12539-014-0191-3

The continuous rise of bacterial resistance against formerly effective pharmaceuticals is a major challenge for biomedical research. Since the first computational studies published seven years ago the simulation-based investigation of antibiotics resistance mediated by multidrug efflux pumps of the resistance nodulation division (RND) protein super family has grown into a vivid field of research. Here we review the employment of molecular dynamics computer simulations to investigate RND efflux pumps focusing on our group’s recent contributions to this field studying questions of energy conversion and substrate transport in the inner membrane antiporter AcrB in Escherichia coli as well as access regulation and gating mechanism in the outer membrane efflux ducts TolC and OprM in E. coli and Pseudomonas aeruginosa .