Homology Modelling

Homology modeling involves taking a known sequence with an unknown structure and mapping it against a known structure of one or several similar (homologous) proteins. It would be expected that two proteins of similar origin and function would have reasonable sstructural similarity. Therefore it is possible to use the known structure as a template for modelling the structure of the unknown structure.

All homology modelling approaches consists of three steps

1. Finding homologus PDB files.
2. Creation of the alignment, using single or multiple sequence alignments. (if more than one known is involved, sometimes the knowns are aligned together, then the unknown sequence aligned with the group; this helps ensure better domain conservation) Analysis of alignments; gap deletions and additions; secondary structure weighting
3. Structure calculation and model refinement

From experience in CASP it has been shown that the two steps are the most important. Given a correct alignment on a related template several methods can produce an accurate model, while without a correct alignment no method can produce a good model.

There are many programs available for homology modelling. The easiest method is to use a webserver such as SWISS-MODELLER , 3D-Jigsaw homology or What-IF

Alternative programs such WHAT-IF as modeller can be run locally on your computer.

Homology modelling for beginners

This part is stoolen from a tutorial in homology modelling written by Gert Vriend. Gert vriend has also create an excellent introductory homology modelling course here

1. Introduction.
2. Professional gambling, the game of 21.
3. Modeling overview.
4. The modelling process.
5. What can be modelled?.
6. Template recognition.
7. Alignment.
8. Improving the alignment using multiple sequences.
9. Improving the alignment using the structure.
10. Alignment correction.
11. Placing new side chains in the structure.
12. Position specific rotamers.
13. Combining multiple side chain conformations.
14. Rotametric entropy.
15. Database retrieval.
16. Modelling loops.
17. Insertions in the model.
18. Verification of the quality of the model.
19. How good are the models actually?.
20. Energy minimisation.
21. Modeling without homology.
22. Concluding remarks.
23. Acknowledgements.
24. References.