An In Silico Approach for Assessment of the Membrane Transporter Activities of Phenols: A Case Study Based on Computational Models of Transport Activity for the Transporter Bilitranslocase

Abstract

Phenols are the most abundant naturally accessible antioxidants present in a human normal diet. Since numerous beneficial applications of phenols as preventive agents in various diseases were revealed, the evaluation of phenols bioavailability is of high interest of researchers, consumers and drug manufacturers. The hydrophilic nature of phenols makes a cell membrane penetration difficult, which imply an alternative way of uptake via membrane transporters. However, the structural and functional data of membrane transporters are limited, thus the in silico modelling is really challenging and urgent tool in elucidation of transporter ligands. Focus of this research was a particular transporter bilitranslocase (BTL). BTL has a broad tissue expression (vascular endothelium, absorptive and excretory epithelia) and can transport wide variety of poly-aromatic compounds. With available BTL data (pKi [mmol/L] for 120 organic compounds) a robust and reliable QSAR models for BTL transport activity were developed and extrapolated on 300 phenolic compounds. For all compounds the transporter profiles were assessed and results show that dietary phenols and some drug candidates are likely to interact with BTL. Moreover, synopsis of predictions from BTL models and hits/predictions of 20 transporters from Metrabase and Chembench platforms were revealed. With such joint transporter analyses a new insights for elucidation of BTL functional role were acquired. Regarding limitation of models for virtual profiling of transporter interactions the computational approach reported in this study could be applied for further development of reliable in silico models for any transporter, if in vitro experimental data are available.