I am working on a ligand that is co-crystalized to parotein, but the ligand is missing some residues that makes it appear as if it was separated into two ligands!
what I need is to connect them into one to run molecular dynamics simulation, what is the best tool to do so, also what are the steps to make sure that it will be mostly accurate?
What I've found immensely useful for this exact purpose is Yasara! You can accomplish everything you've mentioned in the question very easily on this platform. Additionally, you can also run MD simulations. The catch here however is that, Yasara is paid software!
I'd presonally be interested to learn about free options to do this!
Ajay Abisheck Paul George
I did it before, I used Pymol to build the missing residues using Builder, then minimized the ligand via free MAESTRO's selective minimzation, then used avogadro but it was not the best to use.
However, I am still wondering if this was the best mehod or not!
Ahmed samier Mohamed , could you please elaborate on " it was not the best to use", as it would probably help me (and others) understand the challenge better help you on this. I do have a few other questions which would potentially improve my understanding of the system you are trying to model.
- Is your ligand a peptide?
- If yes, does it contain any non-canonical amino acid?
- Is it a cyclic peptide?
In any case, I would not really question your approach, since it is fairly sound and straightforward. In a lot of instances such as these, it is indeed hard to determine or judge the correctness of the approach and solution, since at every step of the way one could question/nitpick your method.
If your ligand is a peptide and you happen to be filling in critical residues that are missing in the crystal structure, you might want to run long (and multiple) simulations to make sure that, if the peptide has to fold further, you've captured its larger conformational space
Ajay Abisheck Paul George
After minimizing my newly linked ligand parts I tried to use UFF in Avogadro to further minimze the structure to reach its best, the results were that Avogaro broke the lignad again, so I decided it is not the best for my experiment.
Replying to your questions:
1-yes it is a peptide ligand.
2-It has a phosphoserine, so yes it has a NSAA
3-it should not be cyclic.
As you said I think running MDS for like 100ns for the ligand, and cluster it picking its best form would give me good reasoning on relying on it after all.
I am trying coot, for now, trying to build these missing residues hopefully it would result in a better ligand conformation, so let's see what will happen!
Ahmed samier Mohamed
If it helps, you could send me your complex with all parts of your ligand correctly filled in, and I can try to minimize the structure for you, in Yasara.
Ajay Abisheck Paul George
Thanks so much for your generous offer,
I did it once again and here is the pipeline:
1-I used Chimera this time and Put the fragments together.
2- then Via the "Join Function" in the structure Build I bonded them at the known atoms.
3- minimized the energy using the minimization tool in Chimera.
4-I used the validation method of Mol-probity, but I still need further modifications to avoid some bad rotamers! I will use for that PHENIX hopefully it will be better!
Thanks again, your replies really helped me out.
Ahmed samier Mohamed no problem at all! Your workflow looks good so far. All the best with the simulations.
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