Homology modeling
From Proteopedia
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Homology modeling has become largely obsolete since the 2020 success of structure prediction by AlphaFold and other AI prediction systems. Rather than starting here, we suggest starting at How To Find A Structure. |
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 gaps in the sequence alignment due to insertions/deletions ("indels"), or portions of the template that lack coordinates due to crystallographic disorder. Provided there is sufficient sequence identity between the query and template (at least 30%), the main chain in homology models is usually mostly correct. However, the positions of sidechain rotamers in homology models are usually unreliable.
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.
