Design of a Three-Dimensional Multitarget Activity Landscape

Abstract

The design of activity landscape representations is challenging when compounds are active against multiple targets. Going beyond three or four targets, the complexity of underlying activity spaces is difficult to capture in conventional activity landscape views. Previous attempts to generate multitarget activity landscapes have predominantly utilized extensions of molecular network representations or plots of activity versus chemical similarity for pairs of active compounds. Herein, we introduce a three-dimensional multitarget activity landscape design that is based upon principles of radial coordinate visualization. Circular representations of multitarget activity and chemical reference space are combined to generate a spherical view into which compound sets are projected for interactive analysis. Interpretation of landscape content is facilitated by following three canonical views of activity, chemical, and combined activity/chemical space, respectively. These views focus on different planes of the underlying coordinate system. From the activity and combined views, compounds with well-defined target selectivity and structure-activity profile relationships can be extracted. In the activity landscape, such compounds display characteristic spatial arrangements and target activity patterns.