BIOACTIVE DIVERSITY AND SCREENING LIBRARY SELECTION VIA AFFINITY FINGERPRINTING

The Similarity Principle provides the conceptual framework behind most modern approaches to library sampling and design. However, it is ofte n the case that compounds which appear to be very similar structurally may in fact exhibit quite different activities toward a given target. Conversely, some targets recognize a wide variety of molecules and th us bind compounds that have markedly different structures. Affinity fi ngerprints largely overcome the difficulties associated with selecting compounds on the basis of structure alone. By describing each compoun d in terms of its binding affinity to a set of functionally dissimilar proteins, fundamental factors relevant to binding and biological acti vity are automatically encoded. We demonstrate how affinity fingerprin ts may be used in conjunction with simple algorithms to select active- enriched diverse training sets and to efficiently extract the most act ive compounds from a large library.