I am trying to perform molecular docking of a ligand composed of a metallic center and an organic moiety that are connected through a non-covalent ion-hydrogen interaction (anion-cation type). The problem is that most docking tools interpret these two parts as separate ligands, which prevents docking the complex as a single entity.
Is there a recommended way to prepare such a complex for docking while preserving the non-covalent interaction?
Would it be appropriate to temporarily add a covalent bond between the metal and organic part to force the docking software to treat them as one ligand, and then adjust this artificially created bond during post-docking analysis?
Any advice or workflow suggestions would be highly appreciated.
Try xtb and the docking module provided in the newest version. The idea behind xtb is completely different and you will need to reduce the protein part by a lot (leaving just a small number of the most important residues) to make a reasonable model of the binding site. Also, the calculations will be much slower and at the end you will obtain just the energy of the entire system (getting interaction energy should also be easy, getting Gibbs free energy of binding rather difficult or impossible for larger systems). The good thing is that the GFN2-xTB is parametrized for most elements, so it should work.
There is no way to make it work in standard docking programs or it will require a lot of work trying to parametrize the system in question.
I have faced a similar problem with non-covalent dimers of organometallic compounds. I was able to use YASARA-Structure to solve the problem by using its feature to fix the structures as rigid molecules, save them in YASARA's YOB format, and carry out the docking in YASARA using its implementation of either Autodock or Vina.
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