AcrAB-TolC is a multidrug efflux transport system in Escherichia coli using the proton gradient between periplasm and cytoplasm, and plays a major role in the intrinsic resistance of Gram-negative bacteria. AcrAB–TolC is a modular-built membrane protein complex transiently assembled from an inner membrane transporter AcrB acting as the pump's engine, an outer membrane channel TolC acting as efflux duct through which substrate is exported from the cell, and an adapter protein AcrA anchored to the inner membrane stabilizing AcrB and TolC interaction and enhancing pump activity. While AcrAB–TolC has been in the intense focus of experimental and computational research, the overall mechanism for the substrate transport is still unclear. How do AcrB and TolC interact ? How does AcrA interacts with AcrB and TolC? How are these interactions involved in substrate export? To solve these question, we performed all-atom molecular dynamics (MD) simulations of AcrAB–TolC embedded in POPE lipid bilayers in solution (over 7 million atoms) using cryoEM structures which have been solved. To the best of our knowledge, this is the first MD simulation of full structure for the AcrA-AcrB-TolC complex.<br/>Recently, we developed FUJI force field for phospholipids (DLPC, DMPC, DOPC, POPC, SOPC, POPE, DOPE, etc) based on general AMBER atom types and original AMBER van der Waals parameters in a unified manner including proteins and nucleic acids. It is known that the interaction between membrane protein and membrane has a non-negligible effect on the dynamics of membrane proteins. In this meeting, we report the results of MD simulations of AcrB transporter or AcrA-AcrB-AcrZ-TolC complex embedded in lipid bilayer as well as effect of dynamics of lipids on transporter stability.

Molecular dynamics simulations of multidrug efflux transport complex AcrAB-TolC embedded in lipid bilayers

256th National Meeting (2018)

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