Do Drugs Have Access to the P-Glycoprotein Drug-Binding Pocket through Gates?

Ricardo J. Ferreira, Maria José U. Ferreira, Daniel J.V.A. Dos Santos

Research output: Contribution to journalArticlepeer-review

21 Citations (Scopus)

Abstract

The P-glycoprotein efflux mechanism is being studied since its identification as a leading protagonist in multidrug resistance. Recently, it was suggested that drugs enter the drug-binding pocket (DBP) through gates located between the transmembrane domains. For both a substrate and a modulator, the potential of mean force curves along the reaction coordinate obtained with the WHAM approach were similar, with no activation energy required for crossing the gate. Moreover, drug transit from bulk water into the DBP was characterized as an overall free-energy downhill process.

Original languageEnglish
Pages (from-to)4525-4529
Number of pages5
JournalJournal of Chemical Theory and Computation
Volume11
Issue number10
DOIs
Publication statusPublished - 31 Aug 2015
Externally publishedYes

Bibliographical note

Publisher Copyright:
© 2015 American Chemical Society.

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