30
and R752 are of particular interest because these residues are also found in the DHT binding pocket
but more importantly, research has been conducted on these residues stating that they are hydrogen
donors/acceptors for hydrogen bonding.
7.1.3
DBD – Hypothesized Binding Pocket
When inputting the DBD PDB file (1R4I), there is no ligand bound to the crystal structure. In
order to create the binding pocket to be used
in the preliminary trials, all possible electrical and
chemical interactions must be evaluated between the AR and the DNA to
make a hypothesized
binding pocket. Table 3 shows the results of the various ligands bound in the DBD with this
hypothesized binding pocket. The ligands used in these models were the same as the LBD
models with the exception of the positive control now being pyrvinium pamoate. This is the
theorized positive control for the DBD as discussed previously. The VLS Scores to
note are for
PP (-22.99), ca27 (-29.34), ca58 (-29.36), and docetaxel (-9.042).
31
Table 3: MolSoft ICM DBD-Pocket Results
In Figure 16, we can see the various ligands bound to the DBD binding pocket.
Analyzing the
positive control (PP), the benzene group is orientated towards the AR and appears to be in close
enough proximity to interact with the residues in the protein. ca27 and its analogs all bound
directly into the binding pocket as that was a requirement for the model, however, they are all
bonding nearer to the DNA and farther away from the AR. This is
unlikely to affect the AR
however further modeling needs to be completed. The negative control also showed much better
binding in these models than the LBD, however, the results are not conclusive enough to state that
the negative control is favorably binding and nullifying the model.
32
Figure 16:
Docking Results for the various ligands in DBD binding pocket. A is PP. 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.
Dostları ilə paylaş: 
