28
Figure 13:
Docking Results for the various ligands in general LBD. A is DHT. B is
ca27. C is ca51. D is ca58. E is ca27 without MA. F is ca27 with OH groups. G is
Docetaxel. F is MG132.
When binding to the entire
pocket with no specifications, these
models are validated by DHT
binding in the exact same location and orientation
as the previous model,
to the DHT binding
pocket. If DHT did not bind to the DHT binding pocket, the validity of this model would be in
question. However, when binding ca27 and its various analogs, they did not show any binding tot
the DHT binding pocket (outlined in blue). Instead, each of the analogs attempted to bind in a
slightly smaller space very near the DHT binding pocket. Further analysis of this new binding site
identified possible chemical bonds that could occur in the area.
In Figure 14, we view a comparison of the original DHT binding pocket to the new ca27 binding
pocket. We can see that the ca27 binding pocket is slightly smaller in size compared to the DHT
binding pocket, however, it is still within the “drug-like” volume and size defined by the software
to be a valid therapeutic target. This second pocket would cause misfolding within the protein and
lead to cell death which explains the experimental results seen in previous research.