Version 1
: Received: 30 August 2018 / Approved: 30 August 2018 / Online: 30 August 2018 (14:43:53 CEST)
How to cite:
Jun Du, J.; Duan, G.; Ji, C.; Song, J.; Zhang, J. Insights from MD Simulation on Na+ Binding and Loop Dynamics in Multidrug Resistance Transporter Norm. Preprints2018, 2018080532. https://doi.org/10.20944/preprints201808.0532.v1
Jun Du, J.; Duan, G.; Ji, C.; Song, J.; Zhang, J. Insights from MD Simulation on Na+ Binding and Loop Dynamics in Multidrug Resistance Transporter Norm. Preprints 2018, 2018080532. https://doi.org/10.20944/preprints201808.0532.v1
Jun Du, J.; Duan, G.; Ji, C.; Song, J.; Zhang, J. Insights from MD Simulation on Na+ Binding and Loop Dynamics in Multidrug Resistance Transporter Norm. Preprints2018, 2018080532. https://doi.org/10.20944/preprints201808.0532.v1
APA Style
Jun Du, J., Duan, G., Ji, C., Song, J., & Zhang, J. (2018). Insights from MD Simulation on Na<sup>+</sup> Binding and Loop Dynamics in Multidrug Resistance Transporter Norm. Preprints. https://doi.org/10.20944/preprints201808.0532.v1
Chicago/Turabian Style
Jun Du, J., Jianing Song and J.Z.H. Zhang. 2018 "Insights from MD Simulation on Na<sup>+</sup> Binding and Loop Dynamics in Multidrug Resistance Transporter Norm" Preprints. https://doi.org/10.20944/preprints201808.0532.v1
Abstract
The multidrug resistance transporter NorM is an important drug resistance pump and plays a critical role in multidrug resistance in bacteria and mammals. In this study we carried out molecular dynamics simulation to study the mechanism of Na+ binding and dynamical structures of two long loops in the substrate-releasing process in substrate binding NorM. Our simulation study identified several key residues (D41, E261 D377) along the Na+ binding pathway and a multi-state ion-binding mechanism is proposed based on the simulation study. In this proposed model, the transport of Na+ is a multi-stage process with D41 being the first station for binding to Na+, followed by Na+ binding to the second station E262 and finally to the cation-binding site of E262 and D377. During the transport of Na+, the transmembrane components TM1, TM7 and TM2 are rearranged to facilitate the ion transport as well conformational changes of NorM to a closed state. Further, substrate-bound simulation revealed that Loop3-4 and Loop9-10 control the substrate-releasing process.
Chemistry and Materials Science, Theoretical Chemistry
Copyright:
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
