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Otherwise known as an ''ab initio'' method, non-template based approaches use a statistical model to fill in the gaps created by the unknown loop structure. Some of these programs include MODELLER, Loopy, and RAPPER; but each of these programs approaches the problem in a different manner. For example, Loopy uses samples of torsion angle pairs to generate the initial loop structure then it revises this structure to maintain a realistic shape and closure, while RAPPER builds from one end of the gap to the other by extending the stem with different sampled angles until the gap is closed.<ref>{{cite journal|last=Holtby|first=Daniel|coauthors=Shuai Cheng Li, Ming Li|title=LoopWeaver – Loop Modeling by the Weighted Scaling of Verified Proteins|journal=Lecture Notes in Computer Science|year=2012|volume=7262|pages=113-126}}</ref> Yet another method is the “divide and conquer” approach. This involves subdividing the loop into 2 segments and then repeatedly dividing and transforming each segment until the loop is small enough to be solved.<ref>{{cite journal|last=Tosatto|first=SC|coauthors=Bindewald, E; Hesser, J; Männer, R|title=A divide and conquer approach to fast loop modeling.|journal=Protein engineering|date=2002 Apr|volume=15|issue=4|pages=279-86|pmid=11983928}}</ref> Even with all these methods non-template based approaches are most accurate up to 12 residues (an amino acid within the loop).
There are three problems that arise when using a non-template based technique. First, there are constraints that limit the possibilities for local region modeling. One such constraint is that loop termini are required to end at the correct anchor position. Also, the [[Ramachandran plot| Ramachandran]] space cannot contain a backbone of [[dihedral angle]]s. Second, a modeling program has to use a set procedure. Some programs use the “spare parts” approach as mentioned above. Other programs use a
==Notes==
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