Computer simulations of the activity of RND efflux pumps

Res Microbiol. 2018 Sep-Oct;169(7-8):384-392. doi: 10.1016/j.resmic.2017.12.001. Epub 2018 Jan 31.

Abstract

The putative mechanism by which bacterial RND-type multidrug efflux pumps recognize and transport their substrates is a complex and fascinating enigma of structural biology. How a single protein can recognize a huge number of unrelated compounds and transport them through one or just a few mechanisms is an amazing feature not yet completely unveiled. The appearance of cooperativity further complicates the understanding of structure-dynamics-activity relationships in these complex machineries. Experimental techniques may have limited access to the molecular determinants and to the energetics of key processes regulating the activity of these pumps. Computer simulations are a complementary approach that can help unveil these features and inspire new experiments. Here we review recent computational studies that addressed the various molecular processes regulating the activity of RND efflux pumps.

Keywords: AcrAB-TolC; Antibiotic resistance; Free energy calculations; Molecular docking; Molecular dynamics; RND efflux pumps.

Publication types

  • Review

MeSH terms

  • Anti-Bacterial Agents / metabolism*
  • Bacteria / chemistry
  • Bacteria / genetics
  • Bacteria / metabolism*
  • Bacterial Proteins / chemistry
  • Bacterial Proteins / genetics
  • Bacterial Proteins / metabolism*
  • Computer Simulation*
  • Membrane Transport Proteins / chemistry
  • Membrane Transport Proteins / genetics
  • Membrane Transport Proteins / metabolism*

Substances

  • Anti-Bacterial Agents
  • Bacterial Proteins
  • Membrane Transport Proteins