In silico pharmacology: Drug membrane partitioning and crossing
Jazyk angličtina Země Nizozemsko Médium print-electronic
Typ dokumentu časopisecké články, přehledy, práce podpořená grantem
PubMed
27378566
DOI
10.1016/j.phrs.2016.06.030
PII: S1043-6618(16)30481-9
Knihovny.cz E-zdroje
- Klíčová slova
- Active transport, Drug-membrane interactions, In silico models, Lipid bilayer membranes, Molecular dynamics, Passive permeation,
- MeSH
- biologický transport MeSH
- buněčná membrána metabolismus MeSH
- cytoplazma metabolismus MeSH
- léčivé přípravky metabolismus MeSH
- léková rezistence MeSH
- lidé MeSH
- lipidové dvojvrstvy metabolismus MeSH
- membránové proteiny metabolismus MeSH
- počítačová simulace MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- přehledy MeSH
- Názvy látek
- léčivé přípravky MeSH
- lipidové dvojvrstvy MeSH
- membránové proteiny MeSH
Over the past decade, molecular dynamics (MD) simulations have become particularly powerful to rationalize drug insertion and partitioning in lipid bilayers. MD simulations efficiently support experimental evidences, with a comprehensive understanding of molecular interactions driving insertion and crossing. Prediction of drug partitioning is discussed with respect to drug families (anesthetics; β-blockers; non-steroidal anti-inflammatory drugs; antioxidants; antiviral drugs; antimicrobial peptides). To accurately evaluate passive permeation coefficients turned out to be a complex theoretical challenge; however the recent methodological developments based on biased MD simulations are particularly promising. Particular attention is paid to membrane composition (e.g., presence of cholesterol), which influences drug partitioning and permeation. Recent studies concerning in silico models of membrane proteins involved in drug transport (influx and efflux) are also reported here. These studies have allowed gaining insight in drug efflux by, e.g., ABC transporters at an atomic resolution, explicitly accounting for the mandatory forces induced by the surrounded lipid bilayer. Large-scale conformational changes were thoroughly analyzed.
INSERM UMR 850 Univ Limoges Faculty of Pharmacy 2 rue du Dr Marcland F 87025 Limoges France
LCSN Univ Limoges Faculty of Pharmacy 2 rue du Dr Marcland F 87025 Limoges France
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