De Novo Fragment Design for Drug Discovery and Chemical Biology.

TitleDe Novo Fragment Design for Drug Discovery and Chemical Biology.
Publication TypeJournal Article
Year of Publication2015
AuthorsT Rodrigues, D Reker, M Welin, M Caldera, C Brunner, G Gabernet, P Schneider, B Walse, and G Schneider
JournalAngewandte Chemie International Edition
Volume54
Start Page15079
Issue50
Pagination15079 - 15083
Date Published12/2015
Abstract

Automated molecular de novo design led to the discovery of an innovative inhibitor of death-associated protein kinase 3 (DAPK3). An unprecedented crystal structure of the inactive DAPK3 homodimer shows the fragment-like hit bound to the ATP pocket. Target prediction software based on machine learning models correctly identified additional macromolecular targets of the computationally designed compound and the structurally related marketed drug azosemide. The study validates computational de novo design as a prime method for generating chemical probes and starting points for drug discovery.

DOI10.1002/anie.201508055
Short TitleAngewandte Chemie International Edition