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.