In silico screening for antibiotic escort molecules to overcome efflux

Sheikh S. Rahman, Ivana Simovic, Simon Gibbons, Mire Zloh

Research output: Contribution to journalArticlepeer-review

6 Citations (Scopus)


Resistance to antibiotics is a growing problem worldwide and occurs in part due to the overexpression of efflux pumps responsible for the removal of antibiotics from bacterial cells. The current study examines complex formation between efflux pump substrates and escort molecules as a criterion for an in silico screening method for molecules that are able to potentiate antibiotic activities. Initially, the SUPERDRUG database was queried to select molecules that were similar to known multidrug resistance (MDR) modulators. Molecular interaction fields generated by GRID and the docking module GLUE were used to calculate the interaction energies between the selected molecules and the antibiotic norfloxacin. Ten compounds forming the most stable complexes with favourable changes to the norfloxacin molecular properties were tested for their potentiation ability by efflux pump modulation assays. Encouragingly, two molecules were proven to act as efflux pump modulators, and hence provide evidence that complex formation between a substrate and a drug can be used for in silico screening for novel escort molecules.

Original languageEnglish
Pages (from-to)2863-2872
Number of pages10
JournalJournal of Molecular Modeling
Issue number11
Early online date8 Feb 2011
Publication statusPublished - Nov 2011


  • Efflux pumps
  • Escort molecules
  • In silico screening
  • MDR
  • Molecular interaction fields
  • Multidrug resistance

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