DOCKing ligands into receptors: The test case of α-chymotrypsin

Structures of 103 ligands previously tested as inhibitors of chymotrypsin catalysis were docked into the active site of the enzyme by use of the dock computer program. The goodness of fit was evaluated according to an approximate Lennard-Jones potential scoring routine. A statistical analysis indicated that dock correctly ranked the database when viewed in terms of a contingency table of four categories: true positives, false positives, true negatives, and false negatives. Eight of the top ten scoring molecules in the computerized docking procedure had been previously reported to be effective competitive inhibitors of chymotrypsin. This agreement between the computer predictions and experimental observations was encouraging and suggests that the dock computer program may be useful in evaluating other receptors for potential binding ligands.