Jump to main content
Jump to site search
PLANNED MAINTENANCE Close the message box

Scheduled maintenance work on Wednesday 27th March 2019 from 11:00 AM to 1:00 PM (GMT).

During this time our website performance may be temporarily affected. We apologise for any inconvenience this might cause and thank you for your patience.


Issue 3, 2014
Previous Article Next Article

Drug promiscuity of P-glycoprotein and its mechanism of interaction with paclitaxel and doxorubicin

Author affiliations

Abstract

P-glycoprotein (P-gp) pumps a broad range of structurally diverse anti-cancer drugs out of cancer cells. Therefore, multi-drug resistance (MDR) in chemotherapy closely correlates with P-gp. However, how this single transport system recognizes different substrates remains unclear. In this study, we attempt to uncover the mechanism of substrate promiscuity of P-gp by atomistic molecular dynamics simulations. Results indicate that different drugs like paclitaxel and doxorubicin approach the putative binding site of P-gp, and the inner residues are found to be important in this process. An obstacle-overcoming process was observed, illustrating that the inner residues are flexible. Interaction energy calculations suggest that the inner residues possess high affinity toward substrates. The cavity of adaptability to accommodate different drugs would help explain why P-gp has so many different substrates.

Graphical abstract: Drug promiscuity of P-glycoprotein and its mechanism of interaction with paclitaxel and doxorubicin

Back to tab navigation

Supplementary files

Publication details

The article was received on 23 Sep 2013, accepted on 23 Oct 2013 and first published on 25 Oct 2013


Article type: Paper
DOI: 10.1039/C3SM52499J
Citation: Soft Matter, 2014,10, 438-445

  •   Request permissions

    Drug promiscuity of P-glycoprotein and its mechanism of interaction with paclitaxel and doxorubicin

    J. Zhang, T. Sun, L. Liang, T. Wu and Q. Wang, Soft Matter, 2014, 10, 438
    DOI: 10.1039/C3SM52499J

Search articles by author

Spotlight

Advertisements