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 language | English |
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Pages (from-to) | 4525-4529 |
Number of pages | 5 |
Journal | Journal of Chemical Theory and Computation |
Volume | 11 |
Issue number | 10 |
DOIs | |
Publication status | Published - 31 Aug 2015 |
Externally published | Yes |
Bibliographical note
Publisher Copyright:© 2015 American Chemical Society.