If the protein structure available is not full and only catalytic site residues with co-crystallized ligand with highest resolution (1-2 A0) is available. I want to know how the energy minimization should be carried out, - does it require ligand to be removed from the protein or should we keep the ligand during EM? In some manuscripts I found EM is done with ligand (only HOH and other nonstandard residues removed) and in manuscripts EM is done with bare protein (only std. residues). I assume that without ligand if EM is done, we should able to get the native form of protein. But if this EM protein is used for docking or MD, ligand may not dock in the proper site. I want to carry out rigid docking with vina and MD with gromacs.
Dear Mohammad,
The protocol you have given is not optimization of protein. My question is optimization of protein to remove the conflicting bonds and to bring few residues in allowed region.
Dear Rajesh,
To optimize with the ligand or without depends on your goals. With this should not be problem. However, there is a problem - what it means to optimize and for what? I rarely use optimization algorithms for such problems, because they are stuck in the nearest local minimum. I believe that it is better to use as optimization the dynamics at low temperature, for example 50-200 K and by using GB model.
Thanks Alexey,
Does it mean, (if we use protein with ligand, a pdb) just deleting the ligand is enough for docking with new compounds? I want to further see the dynamic of new protein-compound complexes with MD. I think it is better to optimize the protein before docking so that I can get reliable docked poses of compound in the binding site. But the problem is if I optimize the protein with ligand in its binding site, the binding site could not be optimized (the binding site may remain adaptive for the ligand). Where as if I optimize the protein without ligand, the binding site also get optimized. Now if I define newly optimized binding site (may be from the native form of protein) and if I make few residues flexible (which are important for the interaction with original ligand), I could get most reliable docking. These are my naive assumptions, I want your views on this and surly you could shade some light on this.
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