A database has been derived from recently reported [60]fullerene derivatives, and their binding scores with HIV-1 PR have been computed using docking techniques. Computational methods have been used to predict which derivatives may have high binding affinities, and for these compounds biological tests have been performed with purified PR. Experimental results confirm the high binding scores of fullerene derivatives predicted from the docking calculations. Our measurements showed that the fullerene derivative (Fmoc-Baa) has about three times better inhibitory binding (K(i) = 36 nM) than the most active fullerene-based inhibitor (K(i) = 103 nM) currently available.