Abstract
Summary The computer program LUDI for the de novo design of protein ligands was extended so that it is now able to take into account the synthetic accessibility of the constructed molecules. As an example, the design of peptides, amides and peptidomimetics using amino acids as building blocks is described. Two new libraries containing natural and non-natural amino acids were constructed for this purpose. Conformational flexibility is taken into account by using multiple conformers for each amino acid. The program was applied to the design of ligands for the enzymes elastase, renin and thermolysin.