Do molecular recognition features (MoRFs) observed in disordered region change their conformation on energy reduction? I have been analyzing MoRF segments in a prokaryotic protein, which are predicted to be helical. However, on subjecting the model to energy minimization, some of these regions appear to assume a b-strand-like conformation when visualized. Is such a thing possible? or is there some error with the predictor? Predictor used was MoRFPRed
What about the confidence level of the prediction? I used to be doing secondary structure predictor (I forgot what software that I'm using) and there's a confidence level (shown by the length of the bar) on every amino acids. If the confidence level is high and the result of your observation shows otherwise there could be some level of inaccuracy whether in the prediction or in the observation.
And how did you do the energy minimization? Is it in vacuo? Or immersed in water and ions?
The confidence level is not clearly mentioned in the result. As for energy minimization, its performed in water.
I just searching through Wikipedia and finally found it, back then I was using PSSpred (http://zhanglab.ccmb.med.umich.edu/PSSpred/). It'll give you not only the prediction, but also the confidence level for every residue. And if you would like to try another alternative then perhaps you wanna check the links in here: https://en.wikipedia.org/wiki/List_of_protein_secondary_structure_prediction_programs
I can give you some advice regarding to the energy minimization. First of all, I would like to highlight when you said appear to assume a b-strand-like conformation when visualized. It seems to me that the polypeptide just fold in a long U shape, but I think it doesn't necessarily to be a beta strand. I think you have to check the hydrogen bond formation between the backbone just to make sure. The second one, I believe it is important to check the Ramachandran plot, to see how many outlier are there. I think it is probable that the conformation are falling into one out of several local minima (when it supposed to fall into the global minima), and Ramachandran plot would show some hint about that. The last one, I think you should read this as it says it is very difficult to predict the disorder region part: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2828120/
It is now quite clear that the disordered regions for the recognition of the many molecular partners (usually the IDPs are HUB proteins) must be subject to other conditions, that is, to have numerous charged residues (thus having a total net charge at neutral pH very high), as well post-translationally modifiable residues in this same region. If this happens the protein assumes a conformation spatially favorable to the interaction. Not forgetting that the most appropriate representation of IDPs is through conformational ensembles because they do not have an unique stable globular structure fixed in time. The organized structure in IDPs is often fluctuating. That said, doing a minimization by means of a software for modeling (e.g., modeler) without water is a result that can have an error of 100%, i.e., senseless. To get a reliable result you have to make structurally reasonable models by means of molecular dynamics in explicit solvent, at neutral pH, or NMR in solution, otherwise, as people say in the US, the model is phoney baloney.
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