Here's what I did. Assuming that you have a part of the protein crystal structure.
In my case, I have an incomplete structure of the protein. Lets say if I have an amino acid (AA) sequence of 520 (full length), I have the pdb for certain domains which are functionally important. So, I went for homology modelling. I used two predictors Robetta and tr-Rosetta. Each predictor will give 5 models, and score accordingly. Normally the first model of robetta or tr-Rosetta is always the best. But in my experience it is not always the case.
Here's what I did to select the best out of 10 models.
As I know the crystal structure of the part of the protein. I compare the
radius of gyration,
secondary structure and
root mean square deviations between the crystal structure (PDB) and the part of the model (Rosetta and tr-Rosetta) whose crystal structure is already known. Then I select the model based on the errors of the measured quantities. I used the priority as follows
secondary structure > radius of gyration > RMSD. I did this for at least 20 proteins and found that it is not necessarily the first model given by a predictor is always the best. I sometimes find the 5th model is the best. And coming to comparison between
tr-Rosetta, I would say it depends on the protein you are modelling. For example, I modelled a
HSP70 chaperone, the Radius of gyration (Rg) given by
tr-rosetta is almost double the Rg given by
Robetta. In this case, it is very clear that
Robetta did a good job. (Because the models given by tr-Rosetta are like spaghetti, you can clearly know once you see).
One more technique you can use to know a good model is from cross linking mass spectrometry. This technique gives a good structural information of which residues are crosslinked by a specific organic molecule. For instance, the commonly used lysine specific reactive organic molecules are
disuccinimidylsuberate (DSS) and bis(sulfosuccinimidyl)suberate (BS(3) ) , By using this chemical, researchers can exactly pinpoint to which lysine residues this DSS has crosslinked. If two lysine residues are crosslinked by a DSS, then it is for sure, they need to be at a certain distance between each other. The distance normally is 26-30 angstroms. Now you look at your models from
tr-Rosetta and see if this distance criteria is maintained or not. If not, discard the model.
As for docking, I used High Ambiguity Driven Docking (HADDOCK), which is a free docking server, which can dock protein-protein, protein-ligand etc..