I have a complex with good energy binding, but this one breaks when I run a MD in namd, the RMSD is about 10 or more. The configure file for namd was maked with gwikMD.
You did not mention what does the complex contain. I am assuming it is a protein-ligand complex. There could be many reasons for failing the system during MD simulations
1. The choice of force field parameters for your model complex, especially ligand.
2. Even though the docking model has good binding energy, there could be some interactions (amino acids) between A and B that may disrupt the dynamics of your complex.
3. The reliability of docking model obtained. What docking tool you have used. Does multiple docking tools/scores result the same complex.
it is really difficult to answer your question without having much information about the system generation, how it is treated, etc
I hope this helps
Suresh Gorle:
1. Yes, it is a protein-ligand complex. The ligand was parameterized with acpype using CHARMM force field
2. There are not nitrogen atoms in the ligand (really I didn't understand this part)
3. I'm working with Autodocktools with a genetic algorithm in vacuum condition. I got similar result in all complexs. I tried with diferent run times (50), evaluation numbers (2500000 and 25000000) and grid boxes size. Then, the best complex with negative energy was analyze in a MD in NAMD with CHARMM force field.
Finally, I obtained similar results for all the dynamics. The complex is unstable and in less than 1 ns the ligand is out, with an RMSD of 10 or more.
Don't worry, it means that your MD simulation is working out to find a much better place for the guest inside the host or maybe outside. If you expect that your ligand stays inside the protein, so why do you run molecular ****dynamics**** simulation?
Fabiola,
Let me clarify the point 2 I mentioned
if the ligand is close to amino acids constituting the active site in your docking model, MD simulations try to find the best position by rearranging the amino acids. This some times result in unstable complex and subsequently increases the RMSD of the system. You can try performing stepwise minimization by restraining the protein first, then the ligand and the whole complex. Then perform simulations on the system by removing the restraints on the ligand first and whole complex. This may result in stable complex and then you can run longer simulations.
Ramin Ekhteiari Salmas, I'm sorry but I'm new in this area. I try to investigate if my protein-ligand complex is stable. I read in many papers that after the docking it is necessary to make an MD to analyze the stability, even more, it was a recommendation for a future publication. So, I try to execute an MD for my complex with the tutorial of namd and qwikMD, but the result is not as expected. I do not know if this is normal or I did something wrong.
I send my configuration files
Suresh Gorle. How much time do you recommend for the minimization and dynamics?
It takes few ns like 1 to 5 ns. If it requires major conformational changes in the active site then you have to go longer time scales.
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