Pharmacophore proponent Jonathan S. Mason, a computational chemist at Bristol-Myers Squibb in Princeton, N.J., discussed at the meeting the advantages of using four centers in a pharmacophore, as opposed to the more traditional three. However, he and others have noted that calculations involving them can be slow. Additionally, problems may arise because multiple pharmacophoric motifs may cause or prevent activity at any particular receptor. Fingerprints are bit strings of zeros and ones unique to each compound, representing yes or no answers to questions about a molecule's properties. The questions can correspond to the axes used in chemistry space.
Fingerprints lend themselves well to similarity analyses.
According to some studies, two molecules have similar biological activity when the Tanimoto coefficient has a value greater than a threshold of 0.7 or 0.8. ArQule uses them to see how much overlap their custom-designed libraries have with other large drug databases. Daylight Chemical Systems in Los Altos, Calif., also uses fingerprint methods in their similarity software. Alain P. Calvet, a researcher at Parke-Davis, in Ann Arbor, Mich., described how fingerprint space can be used to show that a diverse set of reagents doesn't necessarily lead to a diverse set of products. Defining compounds by binding affinity Alexander Tropsha, assistant professor of medicinal chemistry and director of the Laboratory for Molecular Modeling at the University of North Carolina, Chapel Hill, described his unique method of selecting a diverse set of compounds with a technique called simulated annealing.