Dali server: structural unification of protein families

Area of Science:

• Structural bioinformatics
• Computational biology
• Evolutionary biology

Background:

• Protein structure dictates biological function and evolutionary relationships.
• Experimental structure determination is costly and time-consuming.
• Deep learning models, like those in the AlphaFold Database, have expanded structural coverage.

Purpose of the Study:

• To report recent upgrades to the Dali web server for 3D protein structure comparison.
• To enhance the Dali server's capabilities by integrating AlphaFold Database models and protein family annotations.
• To leverage these new features for novel biological discoveries.

Main Methods:

• The Dali server was upgraded to include searchable foldomes from the AlphaFold Database (version 1).
• Structural alignments generated by Dali are now annotated with protein families.
• Comparative analysis was performed using these enhanced features to explore protein evolutionary relationships.

Main Results:

• The Dali server now allows searching of AlphaFold Database foldomes.
• Structural alignments are enriched with protein family information.
• A novel, functionally diverse subgroup within the WRKY/GCM1 protein clan was identified by linking various protein families and uncharacterized proteins.

Conclusions:

• The upgraded Dali server facilitates deeper evolutionary analysis by integrating structural models and family data.
• The discovery of a novel subgroup highlights the power of combining structural comparison with large-scale structural databases.
• These advancements aid in understanding protein function, conservation, and evolutionary shifts.