If the target sequence of amino acids one wishes to obtain a structural model of is very similar to a template protein of known structure, it's possible to obtain the structural model by copying the backbone elements of the template and adding loops and side chains. This is known as comparative protein modelling, knowledge based modelling or homology modelling.
The modelling process coarsely divides into the following steps:
Fully automated programs performing comparative modelling exist
which obtain reasonable results only if template and target
share at least 50 % identical residues in an alignment.
Detection of suitable templates ususally is done by performing a BLAST-search against the sequences in the PDB (Brookhaven Protein Data Bank), the repository for protein-structure obtained by X-ray crystallography and NMR. All sequences in the PDB with an E-value of Blast below a certain treshold are considered as candidates for the template.
The next step consists of aligning target and template sequence.
At this point the modeller has to decide, if
the detected template is suited for the modelling process.
Of course, template and target should share regions of
Taking 100 positions of the alignment into account,
a rule of thumb is, that the alignment at least should contain
30 % identities.
Most important is of course the existence of conserved regions.
A multiple sequence alignment with family members of the template
or several template sequences may be constructed.
Several methods are used for loop building and side chain reconstruction. For example Ramachandran plots compute suited torsion angles in polypeptides, whereat atoms which are supposed to be hard spheres with van der Waals radii are not allowed to collide . Futhermore force field scores are used .
Comments are very welcome.