Predicting the effect of variation on protein structure and function

The effect of genetic variation on protein structure and function varies dramatically depending on the type of protein and the extent of variation. This means that it is difficult to predict the exact effect of sequence variance upon structure, and therefore, function of a protein.

The location of the variation needs to be considered, along with the function of the protein, to help gain an understanding of the effect of a variant on the protein structure and its function.

Visualisation of protein structure

If the protein structure is known, you can find the structure at the Protein Data Bank (PDB). Visualisation of the structure is possible with a number of downloadable programs, for example PyMol and Coot, or on an online viewer, for example the LiteMol viewer used at PDBe.org (see video 1).

With these viewers, you can view the location of a variant residue within the structure and use this information to assess whether this is likely to cause a significant effect in the protein function.

At PDBe.org, on the macromolecules pages for an entry, you can access the Uniprot sequence coverage viewer to find all other entries in the PDB with proteins from that Uniprot ID. This will then show, for each PDB entry, the regions of the sequence for which the structure has been solved. This will also highlight any variants in the structure, as compared to the UniProt sequence.

Learn more about viewing protein structures with PDBe in this webinar.

Continue to the next page to learn about AlphaFold DB, the database of predicted protein structures.