Phyre2.2: A Community Resource for Template-based Protein Structure Prediction

Area of Science:

• Structural biology
• Bioinformatics
• Computational biology

Background:

• Template-based modelling (homology modelling) predicts protein structure using known related structures.
• Recent advances like AlphaFold provide accurate models, even without clear templates.
• Existing tools require users to manually identify suitable templates.

Purpose of the Study:

• To introduce Phyre2.2, an enhanced version of the Phyre2 protein structure prediction portal.
• To integrate AlphaFold models as potential templates within the Phyre2 workflow.
• To improve the usability and comprehensiveness of protein structure modelling.

Main Methods:

• Phyre2.2 automatically identifies suitable AlphaFold models to serve as templates for user-submitted protein sequences.
• The tool searches an expanded template library containing representative structures for all Protein Data Bank (PDB) entries.
• Ranking algorithms are modified to highlight domain-spanning alignments.

Main Results:

• Phyre2.2 now incorporates AlphaFold models, expanding template options for protein structure prediction.
• The template library includes representative apo and holo structures where available.
• Enhanced hit ranking provides clearer insights into domain organization.

Conclusions:

• Phyre2.2 offers a more robust and user-friendly approach to protein structure modelling.
• The integration of AlphaFold models and an expanded template library improves prediction accuracy and scope.
• Phyre2.2 supports batch processing for proteome-scale analysis and is freely accessible.