What is the difference between Haddock 2.4 and 3? I have currently been using Haddock2.4 for protein-peptide docking but want to know if Haddock 3 is a more comprehensive software? Although Haddock scores can’t be correlated to binding affinities, I am wondering if it still ccan be used as an approximation? The restraints and protein is kept the same, the only thing that changes with each docking is the peptide. So far I have had some haddock scores that haven’t correlated with assays I have done. Whereby, I have seen peptides that have a low IC50 have a higher haddock score and vice versa. I am not sure if one factor is the energy minimization of the peptide before docking? Currently I have used Openmm. I am just not 100% sure whether my dockings are accurate due to my preparation of them. Thank you!
General comment, unless the peptide is completely noncompetitive, the IC50 will always be diff than the KD. Comp inhibitors will have higher IC50s than KD, and cooperative binders (uncompetitive inhibitors) will have lower IC50s than KD.
the assays I do are non competitive. I just use a protein enzyme and incubate with my peptide. But I thought there would still be some correlation between that and haddock score
The HADDOCK score is not a proxy of binding affinity… So I would not expect very high correlations.
In some cases it does a good job, in some other not.
If one of the component is constant, e.g. the same receptor, it might do better.
But again it has never been trained / benchmarked against binding affinity data.