CXCR4 is a G protein coupled receptor (GPCR) that has multiple critical functions in normal and pathologic physiology that include regulation of the metastatic behavior of mammary carcinoma, and utilization as a coreceptor for infection by T-tropic strains of HIV-1. Molecular dynamics simulations of CXCR4 were performed in a solvated lipid bilayer to reproduce the microenvironment of this integral membrane protein. The structural basis for the interaction of T140 and AMD3100 with CXCR4 confirms that the mechanisms used by these agents are different. This complementary utilization of molecular, physical, and computation analysis provides a powerful approach to elucidate GPCR conformation and other membrane proteins.

[Proc Amer Assoc Cancer Res, Volume 45, 2004]