Hi everyone ,
For example, I have a posttranslational modified protein sequence (PTM). I have drawn its 3Dmodel by using swiss model workspace and then downloaded this model and attached here for your kind suggestions. I have some questions :
1.how to find out core active site of the model .
2. when succinylation occurs on lysine 23,30,165, what will be the effect on protein structure, active core site or effect on other domains? And how can I guess these effects from the model?
3. Is there any bioinformatics tool via this tool can I understand the effect of succinylation on active core site or other regions of the protein structure?
4.how can I insert succinyl structure on PTM site? I think its protein docking but don't know how to do. kindly guide me.
plz look at the model i have attached for your kind looking.
Kindly help me.
Firstly, the figures you show are they from a known (crystal) structure of your protein? I'm guessing it is as it looks like there is a ligand bound in the active site.
Answers to specific questions:
1. Read the literature on the protein. The structure, if it's a published one from the PDB, might have it annotated. It may be where hte ligand is bound, depending on the ligand.
2. Unlikely to be able to guess from model. Expts are needed. Could try molecular dynamics simulation, but it won't be conclusive.
3. No
4. PTMs are chemical modifications, docking is inappropriate. The structure can be edited to include them, but then will need to be minimised to ensure it makes some sense.
Trying to understand the effect of PTMs on proteins is a large area of research, even for something as 'simple' as phosphorylation. Other PTMs are less well understood.
1. Try submitting your sequence to the MEROPS databse blast search (http://merops.sanger.ac.uk/cgi-bin/blast/submitblast/merops/advanced). It should indicate the active site amino acid residues in red color in the alignment results. Another alternative is doing what Christian suggested: read the literature of the PDB protein that was used as template for modeling your protein.
2. Only way I know is by molecular dynamics. You would need to run one simulation of the protein with succinylation and another one without. For that you need to find parametrization for succinyl molecules. A quick search on google yielded this article: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3715417/
3. Not to my knowledge.
4. The article above should help you with that. Else, the best alternative is to find a PDB protein that contains succinylation and model such molecules to your protein. MODELLER can do this by adding the option "env.io.hetatm = True" in the modeling script.
Dear you have asked too many things in one package, and most of your questions show that apparently your are avoiding literature search. Its ok if you can live this way, all good. Coming to your questions now,
1. You can predict core active site IF there are no information from the homologue PDB structures. Lots of online stuffs are available, but again you need to know literature to identify false positive and real positive residues. If you want to guess your active site with some intuition then the best way is to open your molecule in any visualizer, lets say PyMol etc and apply surface to it, you will see a hole some where :).
2. You can not guess these effects from your model directly. If your protein is a signaling protein then most probably a conformational change will take place once succinylation occurs. I also believe that 23, 30 and 165 probably will lie in a close vicinity to each other, in that case, it is expected that your active site is some where near to these residues. In that case your have perform Molecular Dynamics as suggested by the above two guys.
3. Yes, Molecular Dynamics is the only effective tool currently in the field. If you go for the Molecular dynamics then I am sure it will take lots of your time, as i feel you are new in the field. So to avoid parameterization, search PDB if you can find any succinylated structure and un succinylated structure, do MD for it that will give you a bit of fair idea, otherwise the best option is to go for parametrization.
4. Yes you can dock it. Try online docking programs there are lots of them. If you can do manually then go for autodock or vina.
BTW, the model you attached is a figure not a model. If you just wana simple docking and have difficulty send me your succinate and PDB model i will do for it in free time.
Good Luck in the field.
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