De Novo Fragment Design for Drug Discovery and Chemical Biology. Academic Article uri icon

Overview

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.

publication date

  • October 21, 2015

Research

keywords

  • Death-Associated Protein Kinases
  • Drug Discovery
  • Protein Kinase Inhibitors

Identity

Scopus Document Identifier

  • 84955171484

Digital Object Identifier (DOI)

  • 10.1002/anie.201508055

PubMed ID

  • 26486226

Additional Document Info

volume

  • 54

issue

  • 50