Transmembrane proteins (TMPs), with diverse cellular functions, are difficult targets for structural determination. Predictions of TMPs and the locations of transmembrane segments using computational methods could be unreliable due to the potential for false positives and false negatives and show inconsistencies across different programs. Recent advances in protein structure prediction methods have made it possible to identify TMPs and their membrane-spanning regions using high-quality structural models. We developed the AlphaFold Transmembrane proteins (AFTM) database of candidate human TMPs by identifying transmembrane regions in AlphaFold structural models of human proteins and their domains using the positioning of proteins in membranes, version 3 program, followed by automatic corrections inspired by manual analysis of the results. We compared our results to annotations from the UniProt database and the Human Transmembrane Proteome (HTP) database. While AFTM did not identify transmembrane regions in some single-pass TMPs, it identified more transmembrane regions for multipass TMPs than UniProt and HTP. AFTM also showed more consistent results with experimental structures, as benchmarked against the Protein Data Bank Transmembrane proteins (PDBTM) database. In addition, some proteins previously annotated as TMPs were suggested to be non-TMPs by AFTM. We report the results of AFTM together with those of UniProt, HTP, TmAlphaFold, PDBTM and Membranome in the online AFTM database compiled as a comprehensive resource of candidate human TMPs with structural models. Database URL http://conglab.swmed.edu/AFTM.
