Uddannelses- og Forskningsministeriet- P-glycoprotein inhibition from a molecular basis – development of rational design strategies for P-glycoprotein modulators

P-glycoprotein (P-gp) is a membrane protein responsible for the transport of molecules through biological membranes. P-gp is widely distributed throughout the body and plays a pivotal role in limiting cellular uptake of xenobiotics such as drugs. It is thus of fundamental importance to understand the exact molecular mechanisms of the biological function of P-gp, and especially how to selectively block the function of this protein in order to prevent unwanted drug efflux. However, due to difficulties in obtaining experimental structures of membrane proteins, and especially such proteins in complex with xenobiotics, our current understanding of the exact mechanism of e.g., drug efflux by Pgp
is largely unknown and thus hampers the development of novel drugs related to e.g., cancer therapy. In this research project, we will combine experimental procedures with state-of-the-art simulation and data science approaches to obtain a molecular basis understanding of the biological mechanisms of P-gp.