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Modeling of drug-transporter interactions using structural information
Susanne Winiwarter1, Constanze Hilgendorf
1AstraZeneca R&D Mölndal, DiscoveryDMPK & Bioanalytical Chemistry, SE-431 83 Mölndal, Sweden. susanne.winiwarter@astrazeneca.com
Current Opinion in Drug Discovery & Development
|January 5, 2008
Summary
Drug-transporter interactions significantly impact drug resistance and disposition. Computational modeling aids in understanding these complex interactions, despite challenges like limited structural data.
Area of Science:
- Pharmacology
- Computational Chemistry
- Biophysics
Background:
- Drug-transporter interactions are crucial in multidrug resistance, drug-drug interactions, and drug disposition.
- These interactions involve transport inhibition, efflux, or enhanced cellular uptake.
- Understanding these mechanisms is vital for drug development and personalized medicine.
Purpose of the Study:
- To review recent computational modeling efforts focused on drug-transporter interactions.
- To explain how chemical structure variations influence transporter interactions.
- To elucidate general transporter functions through modeling.
Main Methods:
- Utilizing ligand-based and transporter-based computational methods.
- Employing techniques such as quantitative structure-activity relationship (QSAR) studies, pharmacophore modeling, homology modeling, and molecular dynamics.
- Analyzing existing experimental data on drug-transporter interactions.
Main Results:
- Modeling studies aim to correlate chemical structures with transporter interaction strength.
- These efforts seek to provide insights into the functional mechanisms of drug transporters.
- The review highlights the utility of computational approaches in this field.
Conclusions:
- Computational modeling is a valuable tool for studying drug-transporter interactions.
- Challenges such as limited structural data and complex experimental results persist.
- Continued modeling efforts are essential for advancing our understanding of drug transport phenomena.
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