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

Abstract

Template-based modelling, also known as homology modelling, is a powerful approach to predict the structure of a protein from its amino acid sequence. The approach requires one to identify a sequence similarity between the query sequence and that of a known structure as they will adopt a similar conformation, and the known structure can be used as the template for modelling the query sequence. Recently several approaches, most notably AlphaFold, have employed enhanced machine learning and have yielded accurate models irrespective of whether there is an identifiable template. Here we report Phyre2.2 which incorporates several enhancements to our widely-used template modelling portal Phyre2. The main development is facilitating a user to submit their sequence and then Phyre2.2 identifies the most suitable AlphaFold model to be used as a template. In Phyre2.2 the user searches a template library of known structures. We have now included in our library a representative structure for every protein sequence in the protein databank (PDB). In addition, there are representatives for an apo and a holo structure if they are in the PDB. The ranking of hits has been modified to highlight to the user if there are different domains spanning the sequence. Phyre2.2 continues to support batch processing where a user can submit up to 100 sequences facilitating processing of proteomes. Phyre2.2 is freely available to all users, including commercial users, at https://www.sbg.bio.ic.ac.uk/phyre2/.

Abstract of "Phyre2.2: A Community Resource for Template-based Protein Structure Prediction" by Harold R. Powell, Suhail A. Islam, Alessia David et al., https://doi.org/10.1016/j.jmb.2025.168960, used under its Creative Commons Attribution license (CC-BY); markup removed, otherwise unmodified.