HIV-1 protease is a key drug target due to its role in the life cycle of the HIV-1 virus. Rigidity analysis using the software First is a computationally inexpensive method for inferring functional information from protein crystal structures. We evaluate the rigidity of 206 high-resolution (2 xc3x85 or better) X-ray crystal structures of HIV-1 protease and compare the effects of different inhibitors binding to the enzyme.