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Are there any issues with short sequences?

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Are there any issues with short sequences?

    The Fragment Library used by the Rosetta folding program is generated by using residue substitution profiles with PSI-BLAST to find similar fragment profiles. Very short sequences (less than about 40 residues) are difficult to detect sequence homologs for with reliable confidence with PSI-BLAST, and therefore the fragments library may suffer.

    Additionally, the Rosetta de novo protocol folds two divergent homologous sequences in addition to the query sequence. If PSI-BLAST cannot find any sequence homologs with confidence due to a query being exceptionally short, Rosetta cannot take advantage of multiple homologs, and the modeling may suffer.

    Perhaps most importantly in de novo modeling, the assumption is made that the target protein forms a soluble domain with a hydrophobic core. Short sequences often do not fold up in this fashion, so the energy function used in Rosetta may incorrectly bias the structures to be more compact than they should be for short targets.

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