Exploring structure–activity data using the landscape paradigm

In this article, we present an overview of the origin and applications of the activity landscape view of structure–activity relationship (SAR) data as conceived by Shanmugasundaram and Maggiora. Within this landscape, different regions exemplify different aspects of SAR trends—ranging from smoothly varying trends to discontinuous trends (also termed activity cliffs). We discuss the various definitions of landscapes and cliffs that have been proposed as well as different approaches to the numerical quantification of a landscape. We then highlight some of the landscape visualization approaches that have been developed, followed by a review of the various applications of activity landscapes and cliffs to topics in medicinal chemistry and SAR analysis. © 2012 John Wiley & Sons, Ltd.