Curling of flap tips in HIV-1 protease as a mechanism for substrate entry and tolerance of drug resistance

Background: The human immunodeficiency virus type 1 (HIV-1) protease is an essential viral protein that is a major drug target in the fight against Ac quired Immune Deficiency Syndrome (AIDS). Access to the active site of this homodimeric enzyme is gained when two large flaps, one from each monomer, open. The flap movements are therefore central to the function of the enzym e, yet determining how these flaps move at an atomic level has not been exp erimentally possible.