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. (c) 2005 Elsevier B.V. All rights reserved.