HIV-1 protease (HIV-PR) inhibitors are an essential part of current drug treatments to control HIV infections. Currently used drugs of this type are competitive inhibitors, and their effectiveness is reduced by the appearance of resistant strains of HIV. There is thus strong motivation to study potential binding sites for allosteric HIV-PR inhibitors. Here we report results from all-atom simulations, using molecular dynamics, to investigate the effect of small molecules in contact with a certain region (the �elbow� region) on the structure of HIV-PR. We find that these small molecules can have the effect of closing flaps so as to cover the active catalytic site, and hence that the elbow region is a promising binding site for allosteric HIV-PR inhibitors. Our simulations also suggest how the efficiency of allosteric inhibition depends on the specific conformation of the small molecules. Our data provide valuable information for the design of a new class of HIV-PR inhibitors to help control the current AIDS epidemic.