From Virtual Screening to Bioactiwe Compounds by Visualizing and Clustering of Chemical Space

摘要

Identification and visualization of 'activity islands' in chemical space is presented as a straightforward method for rapid automated identification of bioactive compounds and drug target profiling. We successfully applied this computational technique to finding inhibitors of Helicobacter pylori protease HtrA with new molecular scaffolds, and to deorphanizing of a compound from a combinatorial oxa-diazole library. Bioactive molecules were discovered with minimal experimental effort. The results demonstrate that visualization of 'chemical space' provides an intuitive approach to molecular design and virtual screening in drug discovery, even in the absence of a three-dimensional receptor structure.