ALADDIN: an integrated tool for computer-assisted molecular design and pharmacophore recognition from geometric, steric, and substructure searching of three-dimensional molecular structures

ALADDIN is a computer program for the design or recognition of compounds that meet geometric, steric, and substructural criteria. ALADDIN searches a database of three-dimensional structures, marks atoms that meet substructural criteria, evaluates geometric criteria, and prepares a number of files that are input for molecular modification and coordinate generation as well as for molecular graphics. Properties calculated from the three-dimensional structure are described by either properties calculated from the molecule itself or from the molecule as compared to a reference molecule and associated surfaces. ALADDIN was used to design analogues to probe a bioactive conformation of a small molecule and a peptide, to test alternative superposition rules for receptor mapping of the D2 dopamine receptor, to recognize unexpected D2 dopamine agonist activity of existing compounds, and to design compounds to fit a binding site on a protein of known structure. We have found that series designed by ALADDIN show much more subtle variation in shape than do those designed by traditional methods and that compounds can be designed to be very close matches to the objective.