I have to predict 3D structure of protein with long (70 a.a) N-terminal disorder region. Is there any best method for predicting the fold for this disorder region, or only way is use molecular dynamic simulation?
??? How could you solve such specific issue with molecular dynamic simulation ???
I have just suppose that use molecular dynamic will be useful but I don't know is this approach is correct. Is there any method for predict fold disorder region?
It sounds a little bit counter-intuitive to talk about fold of an ID domain… would you ilke to see if your domain has some secondary structure propensity? transient secondary structures? and/or propensity to be fully extended or populated more compact states? I think that MD alone cannot help that much. Classical FField may work for folded proteins and even if there are some solution that might work for IDPs (see for example the combination of force field/solvent model used here, A Preformed Binding Interface in the Unbound Ensemble of an Intrinsically Disordered Protein: Evidence from Molecular Simulations
Michael Knott, Robert B. Best
Research Article | published 19 Jul 2012 | PLOS Computational Biology), I think the force fields still push too much for overcompaction of the structure.
Then of course you cannot easily used unbiased constant temperature MD since the conformational landscape of an IDP is very complicate. You might try to used REMD to have some ensembles of conformations, but I think that in absence of experimental structural data (as the ones coming from NMR, SAXS, other spectroscopies) that complement the computational information and validate it, to address this class of protein is very complicate and quite unsuccessful by simulations only.
Hi Tomaz
A disordered region do not have a unique structure, but if you are intrested in the bias of the conformation you can sample some of the plausible or estimate some of the conformers by threading, looking for conformations compatible to your sequence.
Visit expasy at http://www.expasy.org/tools/
and search in that page threading. There are some links to servers that can give you
some idea of the possible conformations of the sequence of your interest.
I hope this helps
Greetings
Arturo.
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