Computational Modeling of the Smoothened Receptor

     Smoothened is a 7-transmembrane, GPCR-like protein that serves as a key regulator of the Hh signaling pathway. Multiple small molecule binding sites in both the heptahelical region and the extracellular C-terminal cysteine rich domain (CRD) have been identified. We are using a variety of modeling and molecular dynamics techniques to provide a better understanding of the mechanisms through which small molecules bind to and activate/inactivate Smo. We hope that these studies will enhance our insight into this intriguing receptor.


Video of Smo modeled in a lipid bilayer.



Homology Model of the Human Smoothened CRD.

Figure 2