Simulations of substrate transport in the multidrug transporter EmrD

Joseph Baker, Stephen H. Wright, Florence Tama

Research output: Contribution to journalArticlepeer-review

20 Scopus citations


EmrD is a multidrug resistance (MDR) transporter from Escherichia coli, which is involved in the efflux of amphipathic compounds from the cytoplasm, and the first MDR member of the major facilitator superfamily to be crystallized. Molecular dynamics simulation of EmrD in a phospholipid bilayer was used to characterize the conformational dynamics of the protein. Motions that support a previously proposed lateral diffusion pathway for substrate from the cytoplasmic membrane leaflet into the EmrD central cavity were observed. In addition, the translocation pathway of meta-chloro carbonylcyanide phenylhydrazone (CCCP) was probed using both standard and steered molecular dynamics simulation. In particular, interactions of a few specific residues with CCCP have been identified. Finally, a large motion of two residues, Val 45 and Leu 233, was observed with the passage of CCCP into the periplasmic space, placing a lower bound on the extent of opening required at this end of the protein for substrate transport. Overall, our simulations probe details of the transport pathway, motions of EmrD at an atomic level of detail, and offer new insights into the functioning of MDR transporters.

Original languageEnglish (US)
Pages (from-to)1620-1632
Number of pages13
JournalProteins: Structure, Function and Bioinformatics
Issue number6
StatePublished - Jun 2012


  • Major facilitator superfamily
  • Membrane transporter
  • Steered molecular dynamics

ASJC Scopus subject areas

  • Structural Biology
  • Biochemistry
  • Molecular Biology


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