In drug activity prediction (as in handwritten character recogni(cid:173) tion), the features extracted to describe a training example depend on the pose (location, orientation, etc.) of the example. In hand(cid:173) written character recognition, one of the best techniques for ad(cid:173) dressing this problem is the tangent distance method of Simard, LeCun and Denker (1993). Jain, et al. (1993a; 1993b) introduce a new technique-dynamic reposing-that also addresses this prob(cid:173) lem. Dynamic reposing iteratively learns a neural network and then reposes the examples in an effort to maximize the predicted out(cid:173) put values. New models are trained and new poses computed until models and poses converge.

The task of drug activity prediction is to predict the activity of proposed drug compounds by learning from the observed activity of previously-synthesized drug compounds. Accurate drug activity prediction can save substantial time and money by focusing the efforts of chemists and biologists on the synthesis and testing of compounds whose predicted activity is high. If the requirements for highly active binding can be displayed in three dimensions, chemists can work from such displays to design new compounds having high predicted activity. Drug molecules usually act by binding to localized sites on large receptor molecules or large enyzme molecules. One reasonable way to represent drug molecules is to capture the location of their surface in the (fixed) frame of reference of the (hypothesized) binding site.

The task of drug activity prediction is to predict the activity of proposed drug compounds by learning from the observed activity of previously-synthesized drug compounds. Accurate drug activity prediction can save substantial time and money by focusing the efforts of chemists and biologists on the synthesis and testing of compounds whose predicted activity is high. If the requirements for highly active binding can be displayed in three dimensions, chemists can work from such displays to design new compounds having high predicted activity. Drug molecules usually act by binding to localized sites on large receptor molecules or large enyzme molecules. One reasonable way to represent drug molecules is to capture the location of their surface in the (fixed) frame of reference of the (hypothesized) binding site.

Thomas G. Dietterich Arris Pharmaceutical Corporation and Oregon State University Corvallis, OR 97331-3202 Ajay N. Jain Arris Pharmaceutical Corporation 385 Oyster Point Blvd., Suite 3 South San Francisco, CA 94080 Richard H. Lathrop and Tomas Lozano-Perez Arris Pharmaceutical Corporation and MIT Artificial Intelligence Laboratory 545 Technology Square Cambridge, MA 02139 Abstract In drug activity prediction (as in handwritten character recognition), thefeatures extracted to describe a training example depend on the pose (location, orientation, etc.) of the example. In handwritten characterrecognition, one of the best techniques for addressing thisproblem is the tangent distance method of Simard, LeCun and Denker (1993). Jain, et al. (1993a; 1993b) introduce a new technique-dynamic reposing-that also addresses this problem. Dynamicreposing iteratively learns a neural network and then reposes the examples in an effort to maximize the predicted output values.New models are trained and new poses computed until models and poses converge. This paper compares dynamic reposing to the tangent distance method on the task of predicting the biological activityof musk compounds.