 Specific pockets in the binding site of the HIV protease, often referred to as S1,S1',S2 and S2', recognize hydrophobic amino acids on natural substrates.The potency of inhibitors bearing hydrophobic groups complementing these areas is therefore increased.Some residues in the enzyme binding site are capable of forming hydrogen bonds with hydrophilic groups on the inhibitor, for example with the THF moieties on amprenavir and darunavir.