Dear RG Community,
I am validating my docking protocol by re-docking the co-crystalized ligand into a defined pocket.
After docking, I am getting a pose which is flipped around its axis in 180 degree than that of the co-crystalized one.
Surprisingly, RMSD was also very less (below 1.2 Angstrom) between docked and the co-crystalized poses.
Could you please suggest possible reasons and the solution on it.
Thank you.
Dear Vishal Zambre,
Make sure about your PDB and ligand preparation before Docking. Issues in ligand preparation, such as incorrect atom typing, atom order, or charges can lead to flipped poses. Also check symmetry and chirality, because in some cases, docking algorithms may produce inverted chiral centers. Ensure correct stereochemistry in both co-crystallized and docked poses.
Adjust flexibility, scoring, and search parameters for accurate poses and also avoid over-optimization to prevent false positives. If the binding pocket undergoes substantial conformational changes upon ligand binding, prefer flexible docking or induced fit docking approaches.
You can verify input coordinates and formats for both co-crystallized and docked structures. Additionally, try alternative docking software to assess if the issue persists, as different algorithms may yield varied results.
Conduct post-docking minimization or molecular dynamics simulation to refine docked poses and address inaccuracies introduced in the docking process.
Carefully examine these aspects to identify the cause of flipped poses and implement necessary corrective measures.
Thank You
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