I have modeled a cysteine protease enzyme using different software. Though the model generated from Modeller performed better than the other software, as evaluated by using procheck, Q Means server and MD simulation, I was having doubts about the conformation of a particular residue (tyrosine129) in the active site. The particular tyrosine residue is important as it occupy the active site position and since there is no similar residue in the template (alanine or cysteine), it is hard to predict which one of the conformation generated by the software is correct. Please suggest on what basis should I decide which conformation is stable.
In the picture the tyrosine residue has a different conformation from different models generated from different tools.
You can go for the Rama-chandran plot and other stereo chemical evaluating software (Saves Sever)
You are getting different rotamers of the tyrosine side chain, generated by different tools. In this case you can check it by using SAVES server. You can also check the rotamer library. http://kinemage.biochem.duke.edu/databases/rotamer.php
We have reliable results using the Modeller 9.10 program for model building, Slight changes in the alignment, however, may alter the position of Tyrosine sidechain.
Such is not a error but available search space used by software to generate possible model. Even it may adopt a new conformation each time you generate a new model of the same using modeller thus not a matter of worry.
As far as stability concerns you can go for chi plots of your residue side chain conformation. You can use UCLA SAVES for such purpose (CHI1-CHI2 only). For ligand binding analysis you can use any closer conformation towards your pocket by manually inspecting the model in any viewer. Later in real experiment i.e. flexible docking with Autodock right conformation will be suggested by software with minimum energy binding pose.
As said by others before you might actually have more than one rotamer occurring in your structure or the rotamer might change on ligand binding or during the reaction.
Also you might just want to take a look which rotamer interacts best with the surrounding environment. Can the Tyr form hydrogen bonds? How much solvent exposure would you expect from the rotamers etc.
And finally you seem to not have any experimental data which would allow locking down the position. Determining the 'right' rotamer might simply be out of scope of your methods. After all this is a tiny detail in the structure as a whole, despite potentially being a really important one.
Thank you all for the important inputs. I have got the problem solved.
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