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Even if a sequence does not match any in protein databases, it may still be possible to find a suitable structure using a second technique, fold recognition. For perhaps half or three-quarters of unknown (structurally uncharacterized) proteins, there will be a suitable structure in the database one can use as a basis or template for extrapolating a 3-D model, even in the absence of a sequence match.
"The idea of fold recognition is to turn the folding problem on its head and say, 'Rather than finding a structure that's suitable for the sequence, let's see if we can find whether our sequence fits on any existing structures,' " explains Rob B. Russell, group leader of structural bioinformatics at the European Molecular Biology Laboratory, Heidelberg, Germany. "You thread the sequence onto existing structures and see if those structures bury the sequence's hydrophobic residues well, among a number of other structural considerations."
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