کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
2200260 | 1551277 | 2016 | 7 صفحه PDF | دانلود رایگان |
• P-gp effluxes >200 substrates from the blood-brain endothelium.
• Highly flexible transporter that adopts a variety of conformations.
• Molecular basis for structure-function is still unresolved.
• Mechanism of substrate binding and interactions unresolved.
• We review the role of MD simulations in our understanding of P-gp.
The multidrug transporter P-glycoprotein (P-gp) is expressed in the blood-brain barrier endothelium where it effluxes a range of drug substrates, preventing their accumulation within the brain. P-gp has been studied extensively for 40 years because of its crucial role in the absorption, distribution, metabolism and elimination of a range of pharmaceutical compounds. Despite this, many aspects of the structure-function mechanism of P-gp are unresolved. Here we review the emerging role of molecular dynamics simulation techniques in our understanding of the membrane-embedded conformation of P-gp. We discuss its conformational plasticity in the presence and absence of ATP, and recent efforts to characterize the drug binding sites and uptake pathways.
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Journal: Neurochemistry International - Volume 98, September 2016, Pages 146–152