Alpha&ESMhFolds: An Updated Web Server for the Comparison, Evaluation, and Annotation of Human AlphaFold2 and ESMFold Models

• The DB is aligned with the latest releases of UniProt, PDB, Pfam, and AlphaFold DB. • We allow the comparison of pairs of models predicted with AlphaFold2 (v6) and ESMFold. • We functionally characterize the models by mapping Pfam entries on the structures. • A consensus of Quality Assessment methods allows the selection of the best model. The human reference proteome is routinely modeled with predictive tools such as AlphaFold2 and ESMFold. The two methods, based on different procedures, can behave differently depending on the experimental information available for a protein. We previously released a public database that stores pairs of predicted models, allowing us to obtain insights into the two methods and providing a resource where users can select the better model for downstream analysis. Here, we update the database after the latest release of UniProt (2025_04), we functionally characterise the models by mapping Pfam entries on the 3D structures, and we introduce external quality assessment metrics to evaluate and compare the models. We observe that, regardless of the quality and similarity of the predicted models, both AlphaFold2 and ESMFold converge with high pLDDT values in regions covered by Pfam entries. Alpha&ESMhFolds, including all its features, is freely available at https://alpha-esmhfolds.biocomp.unibo.it/ .