I'm working with a protein that does not have a co-crystallized ligand. How to analyze the best docking pose and validate the docking procedure?
Its tricky,
1) you need to do a literature search to find out the amino acids that, when mutated, change the ligand effect (or for that matter, (in)activate protein). After docking, you need to see whether those amino acids are in contact.
2) you need to use more than 1 docking algorithms, VINA, Swiss-Dock etc. Use consensus here.
3) You can first predict the binding pocket on the target-protein, it will also help to narrow down the target space and ligands.
4) Once docked, you need to cluster the poses to see where most of the ligand bounds.
5) Perform a global dock (use whole protein) first, then local dock later(use selected part of the target). Global dock will give you an idea of where the ligand binds most often, then to further refine the target site, perform a local docking.
6) you need to manually inspect each step, whether the results are sensible.
To analyze and validate docking procedure for a protein with no co-crystallized ligand, you need to find the key residue in the active site or binding site of the protein. After choosing the best pose based on docking score and interactions with key residue, you can perform molecular dynamics to validate the docking procedure.
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