Relax with protein+complex

[Anonymous]

Is it possible to relax the protein_complex i.e protein+cofactor+ligand.
If yes, how should i do it?
Thanks in advance.

-K.Prasanth

[Anonymous]

I am new to rosetta. I’m trying docking.
Before repacking the protein for docking i have to relax the protein pdb(following the manual).
But will this affect docking, i.e will relaxing the protein create a much higher steric interaction (causing high conformational change) when docking is done?

[Anonymous]

Yes, you can relax a protien with a cofactor and ligand. You just have to set up the params file for the ligand and cofactor residues first (you have to do this for *any* use of ligands and cofactors in Rosetta, anyway). The ligand docking documentation probably has the best explanation of it (https://www.rosettacommons.org/manuals/archive/rosetta3.4_user_guide/d4/d47/ligand_dock.html). After you have the params file, you simply need to pass them to relax with the -extra_res_fa flag, and things should work out.

Relaxing probably won’t hurt your docking run. While there is a chance the protein will change in such a way that the docking will now have clashes, there’s an equal chance that your starting structure will have a conformation which will result in clashes when you dock. Actually, as relax will remove issues with the structure, I’d guess you’d be less likely to spuriously reject the correct docking conformation if you prerelax the protein. Using a constrained relax protocol will help more, as it will be less likely to move the protein to a non-native like position.

For ligand docking, you absolutely need to do structure preparation (the without ligand repacking). As ligand docking only repacks in a sphere around the ligand, having unoptimized sidechains can result in problems in search, as ligand positions where the repack sphere overlaps with a structural issue will look artificially better than ones where it doesn’t.

A final note – if you’re trying to emulate a “blind” docking, you don’t want to include the docking partner when you pre-relax the protein. There’s a good chance if you include the partner that you’ll over-optimize to the docked state, resulting in results that are artificially better, and wouldn’t be applicable to a blind docking case.

[Anonymous]

Thanks for your Help

[Anonymous]

Thanks for your Help

[Author]

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