DOCK version

HIV Protease. Docking of the 3D structures of the Cambridge Structural Database into the HIV protease binding site, by shape and to some extent by chemical complementarity, was performed with an early version of the... 

AmpC P-Lactamase. A map of hot spots was constructed from the X-ray structure of AmpC P-lactamase and a university version of the program DOCK was used to search for noncovalent inhibitors in 229,810 compounds of the ACD database. Of 56 tested compounds three had values <650pM, for example, compound 41 Ki = 26pM Fig. 16.6) [117]. The experimental X-ray structure of its complex with AmpC P-lactamase closely resembles the predicted binding mode. 

Furthermore, the models have to be reproducible. The model should give the same result when used by different users in different locations. This fact may lead to a preference toward easier models. Depending on the method for QS AR, some steps may be critical for reproducibility. Indeed, some approaches require manual optimization of the tridimensional structure of the chemical, e.g., in the case of tridimensional descriptors. In other cases, stochastic processes are used. Some more complex models done by skilled operators, such as docking, can be critical. Another source of variability is the software version or brand, even for simple bidimensional descriptors. 

All test set ligands were docked and scored as described in the methods section. For three compounds Auto Dock was not able to find any low energy conformation. A visual inspection of the binding site revealed that these compounds can only bind in a low energy conformation if several amino acids change their side-chain orientation. In the present version of AutoDock receptor flexibility cannot be considered. The remaining compounds were successfully docked by the Auto-... 

T. Ewing, Ed., DOCK User Manual, Version 4.0, Regents of the University of California, San Francisco, 1998. 

---