Comparative or Homology Modelling

If your protein sequence shows significant homology to another protein of known three-dimensional structure, then a fairly accurate model of your protein 3D structure can be obtained via homology modelling. It is also possible to build models if you have found a suitable fold via fold recognition and are happy with the alignment of sequence to structure (Note that the accuracy of models constructed in this manner has not been assessed properly, so treat with caution).

It is possible now to generate models automatically using the very useful SWISSMODEL server.

Some other sites useful for homology modelling include:

Sequence alignments, particularly those involving proteins having low percent sequence identities can be inacurrate. If this is the case, then a model built using the alignment will obvious be wrong in some places. I would suggest that you look over the alignment carefully before building a model.

Note that when using SWISSMODEL it is possible to send in a protein sequence only. I would only recommend doing this if the degree of sequence homology is high (50% or greater) for the above reasons. It is best, particularly if one has edited an alignment, to send an alignment directly to the server.

Once you have a three-dimensional model, it is useful to look at protein 3D structures. There are numerous free programs for doing this, including:

Most places with groups studying structural biology also have commercial packages, such as Quanta, SYBL or Insight, which contain more features than the visualisation packages described above. Crystallographers also tend to use O and FRODO, though these require a lot of experience to use with ease.

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