Topology of HIV-1 protease cavities. On the left: Time-average cavities extracted from the MD simulations represented as green surfaces. The substrates were removed and then the cavities were calculated and averaged. The biggest cavity, in all the systems, corresponded to the active site cleft. The homodimer protease was represented in cartoons colored by chain. Right: Time evolution of the volume of the main cavity (active site) during the MD simulations of the WT and M36I, in complex with the different ligands, colored as Fig.2. The average ±SD values are indicated on the top part of each plot.