Protein protein docking

As first, yes, I mean solvated docking option of HADDOCK server. Because, I read that, when it is turned on, it applies ridig body minimization. Since, one of my proteins will always be mutated (excepting wt complex), I thought that using solvated docking option gives a better result. Also, once I saw a treatment in binding poses with respect to my reference complex (I explained below), I thought it is okay to use solvated docking.

Secondly, I have a reference of wild type complex, from another paper, which was also constructed computationally (Young et al., 2008). On the other hand, I have the wild type structures of both the proteins individually and, I apply mutations to the related one via PyMol.

As input data, I give these two proteins as molecule 1 and molecule 2 at first (By the way, once the addition order of the molecules changes, results also change, this is also confusing for me.). Then, I give information of active and passive residues with respect to the experimental data, in input parameters part. As last, in the docking parameters part, I only turn on solvated docking parameter and change clustering parameters from FCC to RMSD, again with respect to my reference paper (Young et al., 2008).

Additionally, by saying binding energy in my previous message, I did not want to mean HADDOCK score but the value exist in the pdb file itself. Does your docking scores statement also include that binding energy term present in pdb file? I attached a screen shot about it to be more clear for you.

On the other hand, since I don’t have wild type structure of the complex, how am I going to apply your advice? By only applying mutations on the related protein in the way of you said and then loading both the proteins on HADDOCK?

In general keep things simple, i.e. don’t use options if you don’t really know what they are doing.
I would not use solvated docking for this.

Second and more important: Forget about the “binding energy” reported in the header of the PDB files.

It is there for historical reasons, but really has no meaning. We never published anything related to it.

We should probably remove it completely in a future version.

If you want to use something, use the HADDOCK score.

And finally, if you don’t know the structure of the wild type complex, you can indeed only rely on docking.

But I would not have much trust in getting at the end reliable predictions of changes in binding affinities.

You might also try to look at the following paper. Could be interesting for you. We did not test it - so no warranty here.

Jemimah, S., Sekijima, M., & Gromiha, M. M. (2019). ProAffiMuSeq: Sequence-based method to predict the binding free energy change of protein-protein complexes upon mutation using functional classification.

Okay, got it.

I thank you for your answers and advices.