Enzyme-inhibitor interactions docking

Another retrospective analysis of already known H DAC inhibitors was carried out by You et al. [68]. They generated a 3D chemical-feature-based pharmacophore model and compared the ligand-based model with the structural-functional requirements for the binding of the HDAC inhibitors. Using this model, the interactions between the benzamide MS-275 and HDAC were explored. The result showed that the type and spatial location of chemical features encoded in the pharmacophore are in full agreement with the enzyme-inhibitor interaction pattern identified from molecular docking. However, also in this study no experimental validation of the modeling results was provided. 

Scoring of both conformations resulted in conclusion that the first one (A) is correct. Higher than that of conformation B affinity of the inhibitor results from additional strong interaction with Arg359 — similar to that found in glutamate-GS complex.95 In order to support that conclusion several other known inhibitors of GS were docked into the active site of the enzyme and scored with eight different functions. In all cases good correlation was found, which confirmed the correctness of the obtained structures and particularly the correctness of the conformation A of PPT in GS active site. 

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