Positive HADDOCK score for glycosylated protein–protein docking

HADDOCK
1

Hello,

I performed protein–protein docking using HADDOCK2.4. My system includes one glycosylated protein (prepared via CHARMM-GUI) and another non-glycosylated protein (antibody). After docking, I noticed that all top clusters have positive HADDOCK scores, even though the docking seems to converge well (binding pocket is defined in RCSB protein structures and papers).

Could the presence of glycans or their partial parameterization be responsible for these positive scores?

2

Check the components of the score to understand where the positive score comes from.

Could be your restraints.

3

The positive score was indeed caused by the restraints in the system.After reducing them, I’ve now obtained a negative score.

Thank you :slight_smile:

4

You can always refine your model using the refinement server of HADDOCK. This will remove the restraint energy terms and optimise the interface.

Or simply subtract 10% of the restraint energy from the score to get the score without the restraints contribution

5

Thank you for the suggestion, I’ll try refinement server to see differences in scores and poses.

6

Hi

I am facing the same issue while doing protein-protein docking. And, tried refinement of the top cluster after docking. Still getting positive and even more higher positive number for the haddock score. Can you suggest me, exactly how you were able to get negative score after refinement?

7

Dear user,

This probably comes from the definition of restraints.
Please have a look at the score components, and my guess is that you will have a high penalty for unsatisfied restraints.

8

Hi,

I reduced the number of active residues and performed the refinement afterward. If you know the binding pocket, it’s better to include only the key residues. However, you may also subtract 10% of the restraint energy from the total score, as Prof. Bonvin suggested.

9

Yes. It was due to restraints only. It has been resolved now, when I reduced the number of active residues. I am thankful to you for instant response.

10

Hlo, I used the method as you suggested and got the negative score when reduced the active residues. I appreciate your help and thank you so much for sharing the information. Actually, I thought it is not okay to use direct score after 10% of deduction, and to report in article. But thanks to you, it is resolved now !