Identification of substrates of P-Glycoprotein using in-silico methods

The ABC transporter superfamily is one of the largest and abundant families of proteins. It is a large group of proteins that transport a range of substances in cell systems. The ABC transporter P-glycoprotein (ABCB1, P-gp), a polyspecific protein has demonstrated its function as a transporter of hydrophobic drugs as well as transporting lipids, steroids and metabolic products. As well as this, previous studies have shown that P-gp is over expressed in cancerous tissues and plays a role in multidrug resistance. In this study, in-silico methods were used to dock a data set of compounds to P-glycoprotein structures available in the Protein data bank. Binding sites were defined using co-crystallised ligand structures of P-gp and docking energies were calculated using MOE. Statistical models were built to gain a better understanding of how compounds may interact with P-gp. The protein was able to bind to structurally different compounds and results indicate that LogP is the most important factor for drug binding to P-glycoprotein.