I am currently trying to do molecular docking with some software that I have accessibility. The crystal structure of targeted protein has already been published with an occupied inhibitor. Therefore, I have designed several derivative inhibitors and I want to predict which could be a better one in term of binding energy. After trying several docking, it seem like the pose of the ligand doesn't quite realistic, where the main scaffold normally has fixed location where to bind, but the docking results show a weird orientation of binding. The question here is is there any software or any way to fix the main scaffold to oriented the way it show in the crystal structure why leave some part to be flexible for alterative docking?
Hi Danko,
Molegro virtual docker can do constraint docking. See the appended manual.
http://www.softpedia.com/get/Science-CAD/Molegro-Virtual-Docker.shtml
Yes you have option in autodock setting the rotatable bonds, root atoms etc .. http://autodock.scripps.edu/faqs-help/faq/how-should-i-prepare-a-ligand-for-docking-with-autodock ..also u have options Schrödinger in ligprep option..
I agree with Rudy J Richardson, Autodock can solve your problem. Using Autodock you can fix the torsional bonds and can consider only the active moiety of receptor protein and rest can be flexible.
Fixing the torsion isn't going to fix the binding location of the part of that ligand, is it?
The problem here is that we know the exact location where part of the ligand is occupied in the crystal structure, and when I tried to dock a ligand that we already have the solved structure, I couldn't get any pose that is close to what we have seen in the actual crystal structure.
It was not quite clear in your postings if you had tried redocking a ligand to the receptor starting with the crystal structure of the ligand-receptor complex. This is a good way to start, in order to determine how well your docking software is working in your hands.
Which docking software are you using? Consult the documentation of that software for details about redocking before undertaking docking with new ligands.
Be sure also that you are following correct procedures for preparing the receptor and ligand for docking as well as setting up the simulation cell properly.
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