If a 3D protein is obtained with the inhibitor complex, its wild-type size may change completely. In this case, it seems correct to investigate the binding mode with the inhibitor molecule. If the protein to be investigated has only an inhibitor complex, what protein should I select in the PDB and in my activator molecule research, and what path should it follow?
So you don't have any PDB structures with activator? If they are not available, you should first find in literature if there is any specific conformational changes for activator and then modulate it on your own (actually you can move aminoacids manually) and then perform molecular dynamics to relax your system. Or you can try to dock activator in native protein structure and then perform MD to generate more states of your systems. If MD would not be enough, you could try to use metadynamics.
Yes. There is not structure in PDB with its activator but Solely with inhibitor complex. How about the predicted its 3D structure of the target protein to analysis for the activators?. So, we can see the difference with wild type and the Pdb structure complex with inhibitors
Yes predicting 3D structure without the inhibitor can work and may provide some insights, but i agree with Alisa Gorislav that docking your activator to the binding pocket. Even if it binds with low energy, and using that structure for molecular dynamics simulations might provide you with a conformation that favors the activation molecule, if that exists.
Sometimes, the protein can be totally different when its inhibitor binds to the protein. I mean the cavity might be totally different. The protein can turn into from Z to N form. But I need Z form which is nature form. Targeting the cavity of inhibitor how such a strategy is I am not sure yet.
Nail Besli Yes you are absolutely correct about the change in conformation of the protein when bound to two different molecule types. However, if you have no structural information available for the conformation with the activator, but have the information for the inhibitor binding.
Molecular dynamics can be a good way to gain some insights of how these conformations change when your protein is unbound (WT), bound to inhibitor and bound to the activator.
This comparative analysis of the structural transitions on a free energy landscape may provide you with detailed conformational transitions that are playing roles. It might be external factors too like salt concentration, pH temperature and so on.
Further, you may use this information to validate your results experimentally and if the changes are adequate you can measure them using fluorescence spectroscopy and circular dichroism spectroscopy experiments.
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