The MD simulations using gromacs 96 force field was done on a compound obtained after semi-flexible docking and flexible docking. The protein was also simulated in water. Comparing the docking results with the original protein structure the total energy was high, so should I conclude that after docking the structure was unstable?
Hello.
If i understand your question correctly, you have performed MD after docking. If so, it is to expect changes in energy due to ligand interaction with protein (which will react to the presence of the ligand).
Another approach is for you to do MD first, relax the protein, and then perform the docking in the equilibrated structure. If you make flexible docking first, only sidechains will be flexible, and when you put the whole system into MD, the whole protein will react to that modification.
Try first to do MD, then docking.
Best regards,
Ricardo Ferreira
OK sir, I WILL try to do other way too, but in case semi-flexible docking i can just say that compound activates the protein-ligand complex or show strong interaction with complex so is high energy ????
Hello.
It's rather difficult to say. It could be yes, but it could also mean that the binding pose and the sidechain orientation, although good for the ligand, it's not ideal for the system. It will depend on the system, because it is to be expected an energetic barrier, but it cannot be calculated like that. Only with metadynamics or free energy profiles.
Best regards,
Ricardo
Hi,
You should first generate the stable conformation of the protein by performing long MD. The stable backbone conformation can be used now for docking. The high energy is due to the equilibration articrafts in side chains as suggested by Dr. Richardo. After MD simulation, you can go for docking followed by MDS of complex and BE calculation.
Best regards
Bikash
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