Computational Molecular Docking Models and Design of Diarylpentanoids for the Androgen Receptor

 7
 
Results 
7.1
 
MolSoft ICM-Pro 
The outputs for MolSoft are classified into 4 categories; the LBD, the generalized LBD, the 
DBD, and the generalized DBD.
7.1.1
 
LBD – DHT Binding Pocket 
The first step is to verify that the binding is occurring in the correct location (aka, to the DHT 
binding pocket). Figure 11 shows the original, pre-bound DHT ligand found in the crystal 
structure for the 2ama file. This was then superimposed with the same DHT ligand that was 
Figure 11:
 
DHT crystal structure and DHT ligand bound to the DHT binding pocket in 
the LBD 
bounded to the ligand with the software.

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We can see that they are both in the exact same position and orientation which is indicative that 
our model is running accurately in relativity to the real-world data already collected. 
Table 1 shows the results of the various ligands in the LBD-DHT binding pocket.
Table 1: MolSoft ICM LBD-DHT Binding Pocket Results 

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The various ligands are DHT (the positive control as it is the natural ligand for the AR in the 
DHT binding pocket), ca27 (our molecule of interest) and its various analogs, docetaxel 
(negative control, binds to tubulin which is part of the cytoskeleton), MG132 (another negative 
control which binds to the proteasome), and R1881 (a more stable structural analog of DHT used 
in lab work). The values of significance are the VLS Scores for DHT (-33.08), ca27 (-18.42), 
ca58 (-31.69) and docetaxel (264.1).
Figure 12:
 
Docking Results for the various ligands in LBD-DHT binding pocket. 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. 
It is important to note that in the ca27 model, the hydroxyl groups are pointed towards each other.
This is an unfavorable electrical interaction as they are both negatively partially charged.
However, we can then see ca58 and its hydroxyl groups are facing opposite directions. This is a 
much more favorable interaction and is the most probable reason as to why ca58 had such a 
favorable binding score.

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