Efflux pump-mediated antibiotics resistance: insights from computational structural biology.
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.
Computational Structural Biology, Department of Life Science Informatics B-IT, Life & Medical Sciences Institute, University of Bonn, 53113, Bonn, Germany.
Nadine
N
Fischer
Martin
M
Raunest
Thomas H
TH
Schmidt
Dennis C
DC
Koch
Christian
C
Kandt
D001425:Bacterial Outer Membrane Proteins / Q000378:metabolism; D003198:Computer Simulation; D024901:Drug Resistance, Multiple, Bacterial; D004926:Escherichia coli / Q000187:drug effects* / Q000378:metabolism; D029968:Escherichia coli Proteins / Q000378:metabolism; D026901:Membrane Transport Proteins / Q000378:metabolism; D008968:Molecular Conformation; D056004:Molecular Dynamics Simulation; D011522:Protons; D011550:Pseudomonas aeruginosa / Q000187:drug effects / Q000378:metabolism; D012984:Software
D001425:Bacterial Outer Membrane Proteins; D029968:Escherichia coli Proteins; D026901:Membrane Transport Proteins; C402263:OprM protein, Pseudomonas aeruginosa; D011522:Protons; C073126:tolC protein, E coli