A physical model of non-specificity in P-glycoprotein´s selection of substrates

P-glycoprotein (P-gp) can pump a wide variety of structurally unrelated compounds out of cells. However the mechanism of this pumping action remains uncertain. Based on the view that the basic interaction between biological molecules is electric and the change of free energy decides the direction and limit of a reaction, using Debye-Hückel theory and incorporating the simplified structured model of P-glycoprotein, the change of electrostatic free energy in the process of substrates entering the lumen of P-glycoprotein is induced. It is proposed that the main reason of substrates entering the lumen of P-glycoprotein with a high effectiveness is the action of electrostatic free energy. The energy minimum of transporting a substrate is obtained, which has the same order as the energy from one ATP hydrolyzed. It is illustrated that one ATP needs to be hydrolyzed per substrate transported. Two indirect ways to inhibit the action of P-glycoprotein multidrug resistance are proposed.