The Binding Mode of the Sonic Hedgehog Inhibitor Robotnikinin, a Combined Docking and QM/MM MD Study.

ABSTRACT: Erroneous activation of the Hedgehog pathway has been linked to a great amount of cancerous diseases and therefore a large number of studies aiming at its inhibition have been carried out. One leverage point for novel therapeutic strategies targeting the proteins involved, is the prevention of complex formation between the extracellular signaling protein Sonic Hedgehog and the transmembrane protein Patched 1. In 2009 robotnikinin, a small molecule capable of binding to and inhibiting the activity of Sonic Hedgehog has been identified, however in the absence of X-ray structures of the Sonic Hedgehog-robotnikinin complex, the binding mode of this inhibitor remains unknown. In order to aid with the identification of novel Sonic Hedgehog inhibitors, the presented investigation elucidates the b

SUBMITTER: Hitzenberger M 

PROVIDER: S-EPMC5660280 | biostudies-literature | 2017

REPOSITORIES: biostudies-literature