Journal
FRONTIERS IN CHEMISTRY
Volume 5, Issue -, Pages -Publisher
FRONTIERS MEDIA SA
DOI: 10.3389/fchem.2017.00076
Keywords
sonic hedgehog (Shh); QM/MM; robotnikinin; sonic hedgehog inhibitor; metalloproteins; density functional theory; docking studies; molecular dynamics simulation
Categories
Ask authors/readers for more resources
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 binding mode of robotnikinin by performing an extensive docking study, including subsequent molecular mechanical as well as quantum mechanical/molecular mechanical molecular dynamics simulations. The attained configurations enabled the identification of a number of key protein-ligand interactions, aiding complex formation and providing stabilizing contributions to the binding of the ligand. The predicted structure of the Sonic Hedgehog-robotnikinin complex is provided via a PDB file as Supplementary Material and can be used for further reference.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available