Homology modeling

From Proteopedia

Jump to: navigation, search

Homology models, also called comparative models, are obtained by folding a query protein sequence (also called the target sequence) to fit an empirically-determined template model. The registration between residues in the query and template is determined by an amino acid sequence alignment between the query and template sequences.

Imagine that the template’s polypeptide backbone is a folded glass tube. Now imagine that the query sequence is a thin metal chain that can be pulled through the tube. The chain (query) will adopt the same fold as the tube (template). The sequence alignment specifies how far the chain should be pulled into the tube; that is, how the residues in the query sequence match up with the structure of the template.

Errors or uncertainties in the sequence alignment result in errors or uncertainties in the homology model. Portions of the query sequence cannot be modeled reliably when there are Insertions/deletions in either sequence, or portions of the template that lack coordinates due to crystallographic disorder. Provided there is sufficient sequence identity between the query and template, the main chain in homology models is usually mostly correct. However, the positions of sidechains in homology models are usually incorrect.

Nevertheless, homology models are useful for seeing low-resolution features, such as which residues are on the surface or buried, which are close to other features of interest (such as a putative active site), and the overall distribution of charges and evolutionary conservation.

If you wish to make a homology model, please see Practical Guide to Homology Modeling.

See Also

Proteopedia Page Contributors and Editors (what is this?)

Eric Martz

Personal tools