Computational approaches to modeling drug transporters.
Computational modeling has advanced our understanding of drug absorption, tissue distribution, excretion and toxicity profiles by providing both direct and indirect knowledge of drug-transporter interactions that would otherwise be unavailable using experimental methods. Currently, two complementary approaches are available in modeling transporters: substrate-based and transporter-based methods. The transporter-based approach directly predicts the transporter's three-dimensional structure to assist in understanding the drug transport process, whereas substrate-based models infer such information by studying a group of substrates or inhibitors with measured activities. In this review, the available strategies in both transporter-based and substrate-based approaches are explained and illustrated with applications and case studies. With increasing computational power and continuously improving modeling algorithms, computational techniques can assist in further understanding transporter-substrate interactions as well as, the optimization of transporter-directed drug design.
Chang
Cheng
C
Department of Pharmaceutical Sciences, University of Maryland, Baltimore, MD 21201, USA.
Swaan
Peter W
PW
D000465:Algorithms; D000818:Animals; D019295:Computational Biology / Q000379:methods; D015195:Drug Design; D006801:Humans; D026901:Membrane Transport Proteins / Q000737:chemistry* / Q000378:metabolism; D008956:Models, Chemical; D004364:Pharmaceutical Preparations / Q000737:chemistry* / Q000378:metabolism; D011487:Protein Conformation; D021281:Quantitative Structure-Activity Relationship
D026901:Membrane Transport Proteins; D004364:Pharmaceutical Preparations