Modeling of drug-transporter interactions using structural information

Abstract

Drug-transporter interactions have recently been demonstrated to play an important part in multidrug resistance, drug-drug interactions and drug disposition. Such interactions can occur as inhibition of transport, efflux out of cellular systems or enhanced transport into cellular systems. Modeling efforts are currently being undertaken using both ligand- and transporter-based methods, such as (3D) quantitative structure-activity relationship studies, pharmacophore modeling, homology modeling and molecular dynamics studies. The aim of these efforts is to explain how differences in chemical structures either enhance or weaken interactions with the transporter, or to elucidate how the transporter functions in general. This review summarizes recent modeling efforts in the light of difficulties such as the lack of X-ray crystal structures and the complexity and inconsistency of available experimental data on drug-transporter interactions.