Knowledge of a protein’s structure can provide important insights into the mechanism of its function and the likelihood that the stability and/or function of the protein will be affected by genetic variations. For example, structural analyses can provide critical insights into which genetic variants are likely to be disease associated due to their probable impact on protein stability, folding or function. This is central to prioritisation of which variants require detailed study or could act as valid biomarkers. For example, structural data can determine whether residue mutations are likely to cause cavities in a protein, steric clashes or change the electrostatic environment mediating a protein’s function. Structures can also enable detailed understanding of residue sites performing the molecular function and sites involved in interactions with ligands and protein partners acting in the same biological process or signalling pathway. This data is valuable for drug design.
For many organisms only a small proportion of proteins have structures determined, on average less than 10%. To increase this structural coverage, the ELIXIR-UK tools and resources (CATH-Gene3D, JALVIEW/JPRED/Dundee Resource, PHYRE2) will provide information on predicted secondary structures and disordered regions (JPRED/Dundee Resource) and structural annotations for proteins in more than 2000 genomes (CATH-Gene3D). They will also provide predicted 3D structures for query proteins and for proteins from key model organisms including human, mouse and arabidopsis (PHYRE2).
Our resources will also provide information on structural families to aid detection of conserved structural features. Intuitive visualisations of multiple sequence alignments of protein sequences will be available (JALVIEW) together with information on conserved residues mapped to protein structures (CATH-Gene3D), thus allowing analyses of the proximity of residue mutations to conserved sites or known functional sites.