ANTI-HIV STRATEGY

Abstract

AN AMALGAM OF COMPUTER modeling and experiment has yielded insights on the inner workings of a protein vulnerable to HIV and the molecules that can block the virus. The protein, known as CCR5, belongs to the family of G-protein-coupled receptors (GPCRs). HIV binds to CCR5 to gain access to immune cells. At last week's ACS national meeting in Atlanta, Debananda Das, a computational chemist at the National Institutes of Health, reported that molecules that inhibit CCR5 predominately bind in a large lipophilic pocket on the upper transmembrane portion of the protein (J. Biol. Chem., published online Feb. 13, dx.doi. org/10.1074/jbc.M512688200). Das, in a group headed by NIH retrovirologist Hiroaki Mitsuya, studied the binding of three CCR5 inhibitors, including the promising drug aplaviroc, with dozens of CCR5 mutants. They used that data to develop a computer model of the structure of the CCR5 binding site/inhibitor complex and the key binding interactions. Because no crystal ...