 It should also be considered that the loops in proteins may not be well-structured and therefore have no one conformation that could be predicted; NMR experiments indicate that solvent-exposed loops are "floppy" and adopt many conformations, while the loop conformations seen by X-ray crystallography may merely reflect crystal packing interactions, or the stabilizing influence of crystallization co-solvents.As mentioned above homology-based methods use a database to align the target protein gap with a known template protein.A database of known structures is searched for a loop that fits the gap of interest by similarity of sequence and stems (the edges of the gap created by the unknown loop structure).