In silico pharmacology: Drug membrane partitioning and crossing
Language English Country Netherlands Media print-electronic
Document type Journal Article, Review, Research Support, Non-U.S. Gov't
PubMed
27378566
DOI
10.1016/j.phrs.2016.06.030
PII: S1043-6618(16)30481-9
Knihovny.cz E-resources
- Keywords
- Active transport, Drug-membrane interactions, In silico models, Lipid bilayer membranes, Molecular dynamics, Passive permeation,
- MeSH
- Biological Transport MeSH
- Cell Membrane metabolism MeSH
- Cytoplasm metabolism MeSH
- Pharmaceutical Preparations metabolism MeSH
- Drug Resistance MeSH
- Humans MeSH
- Lipid Bilayers metabolism MeSH
- Membrane Proteins metabolism MeSH
- Computer Simulation MeSH
- Check Tag
- Humans MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Review MeSH
- Names of Substances
- Pharmaceutical Preparations MeSH
- Lipid Bilayers MeSH
- Membrane Proteins 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
References provided by Crossref.org
Computational Methods for Modeling Lipid-Mediated Active Pharmaceutical Ingredient Delivery
Oxidative Stress Evaluation in Ischemia Reperfusion Models: Characteristics, Limits and Perspectives
