Dear researchers and scientists
I did a partial docking experiment to learn the basics of using an internet server. (Seamdock). Two ligands, the first is known to inhibit the target protein and the other to test. Both gave similar results of docking affinity. But the first ligand showed hydrogen bonds with the macromolecule, while the second has only hydrophobic interaction. How do I judge these results? I will attach the files.
And if there is a direct forum for specialists, please guide me
@Ahmed Shaker Ali
Hi,
If the first ligand is known to inhibit the target protein, then your results seem to validate the fact by showing specific hydrogen bonds (the stronger covalent bonds) with the target protein to inhibit the protein's further biological activities. As far as docking affinity is concerned, different tools have different approaches to rank the ligands where mostly these smaller sized ligands do not vary much.
So, it is important to consider the parameters including affinity, types of interactions, number of populations in a single cluster to identify the most suitable ligand binding mode. Also you can compare with the existing experimental data (if any).
You need to compare your results with the experimental data (literature, previous reports, crystal structure, mutation related studies that abolish the ligand binding etc) and see how your results are overlapped/different.
I generally recommend to use more than one server/software to dock and compare the results with each other and with the experimental data. Use the one who has better match with the exp. data. If the exp data is unavailable, then you can go for multiple servers/software, cluster independent results, and compare them to see what is the prevalent binding pose.
Just to make sure the docking results, you can compute the binding pocket and druggability with online servers. It will give you an idea whether these positions are fine and expect-able.
The docking servers/softwares rank the binding pose with some criteria so their scores are crude. If you interested to calculate the binding energy, then MD simulation with free energy calculation has to be carried out.
Ahmed Shaker Ali
As you have mentioned that you have used SeamDock for your docking study. But SeamDock only provides a web-based GUI for docking studies based on different docking algorithms like (autodock, vina, and others).
So, I am not sure you took which of the algorithm for the docking study.
Second these algorithms are semi-rigid in nature taking receptor (protein) as a rigid (non-flexible) entity while ligand is docked as flexible compounds with a limited number of torsions. Hence, your result is limited to the frozen structure of the protein.
I will suggest you to re-perform the docking study using other docking tools. Also, check the binding stability of both dock compounds using molecular dynamic simulation, and calculate free binding energy, which will give you perfect idea and result data to compare between both.
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