P-glycoprotein (P-gp) is a multidrug transporter that catalyzes the transport of a substrate. To elucidate the underlying mechanism of this type of substrate transport, we performed molecular dynamics (MD) simulations using the X-ray crystal structure of P-gp, which has an inward-facing conformation. Our simulations indicated that the dimerization of the nucleotide binding domains (NBDs) is driven by the binding of ATP to the NBDs and/or the binding of the substrate to a cavity in the transmembrane domains (TMDs). Based on these results, we discuss a role of ATP in the allosteric communication that occurs between the NBDs and the TMDs. (C) 2013 Elsevier B.V. All rights reserved.