Finally, X-ray crystallography of 35a in a complex with the enzyme validated our hypothesized binding mode and identified Lys554 as a new target-binding site available for DPP-4 inhibitors.
The inhibitor binding site identified in these docking simulations and importantly the mode of binding, builds on the previous knowledge we have concerning the location at which these compounds act, which is currently limited.
Although we do not have crystallographic data to support the binding modes of the known PDGFRα inhibitors, the docked pose of these type-II ligands are similar to the crystallographic binding pose identified in other known crystal structures.
Two different binding modes were identified using -doxanthrine or SKF89626 in the modeling procedure.
With the aim to predict the most plausible binding mode of the identified inhibitors in this work and to rationalize their structure activity relationship (SAR), molecular docking was performed in the COX-2 active site.
Docking analysis has been carry out in order to identify the binding mode in the active site, and to explain the observed selectivities.
The benefit of docking is to identify the binding mode of ligands in the binding pocket of protein through specific key interactions and to predict the binding affinity between the protein-ligand complexes [ 32].
The differences in binding modes of the identified inhibitors in the active sites of Cdc25A and B are addressed in detail.
However, no binding media could be identified in our studies.
DOI: http://dx.doi.org/10.7554/eLife.01519.015 10.7554/eLiFigure19.016 Figure 3 figure supplement 2. Mutational data on the earlier identified binding modes in DTD.
