Chemspace Atlas: Multiscale Chemography of Ultralarge Libraries for Drug Discovery.

ABSTRACT

Nowadays, drug discovery is inevitably intertwined with the usage of large compound collections. Understanding of their chemotype composition and physicochemical property profiles is of the highest importance for successful hit identification. Efficient polyfunctional tools allowing multifaceted analysis of constantly growing chemical libraries must be Big Data-compatible. Here, we present the freely accessible ChemSpace Atlas (https//chematlas.chimie.unistra.fr), which includes almost 40K hierarchically organized Generative Topographic Maps (GTM) accommodating up to 500 M compounds covering fragment-like, lead-like, drug-like, PPI-like, and NP-like chemical subspaces. They allow users to navigate and analyze ZINC, ChEMBL, and COCONUT from multiple perspectives on different scales from a bird's eye view of the entire library to structural pattern detection in small clusters. Around 20 physicochemical properties and almost 750 biological activities can be visualized (associated with map zones), supporting activity profiling and analogue search. Moreover, ChemScape Atlas will be extended toward new chemical subspaces (e.g., DNA-encoded libraries and synthons) and functionalities (ADMETox profiling and property-guided de novo compound generation).