De Novo Fragment Design for Drug Discovery and Chemical Biology.

Journal Article (Journal Article)

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.

Full Text

Duke Authors

Cited Authors

  • Rodrigues, T; Reker, D; Welin, M; Caldera, M; Brunner, C; Gabernet, G; Schneider, P; Walse, B; Schneider, G

Published Date

  • December 2015

Published In

Volume / Issue

  • 54 / 50

Start / End Page

  • 15079 - 15083

PubMed ID

  • 26486226

Electronic International Standard Serial Number (EISSN)

  • 1521-3773

International Standard Serial Number (ISSN)

  • 1433-7851

Digital Object Identifier (DOI)

  • 10.1002/anie.201508055


  • eng