PT - JOURNAL ARTICLE AU - Michael Bernhofer AU - Christian Dallago AU - Tim Karl AU - Venkata Satagopam AU - Michael Heinzinger AU - Maria Littmann AU - Tobias Olenyi AU - Jiajun Qiu AU - Konstantin Schütze AU - Guy Yachdav AU - Haim Ashkenazy AU - Nir Ben-Tal AU - Yana Bromberg AU - Tatyana Goldberg AU - Laszlo Kajan AU - Sean O’Donoghue AU - Chris Sander AU - Andrea Schafferhans AU - Avner Schlessinger AU - Gerrit Vriend AU - Milot Mirdita AU - Piotr Gawron AU - Wei Gu AU - Yohan Jarosz AU - Christophe Trefois AU - Martin Steinegger AU - Reinhard Schneider AU - Burkhard Rost TI - PredictProtein – Predicting Protein Structure and Function for 29 Years AID - 10.1101/2021.02.23.432527 DP - 2021 Jan 01 TA - bioRxiv PG - 2021.02.23.432527 4099 - http://biorxiv.org/content/early/2021/02/24/2021.02.23.432527.short 4100 - http://biorxiv.org/content/early/2021/02/24/2021.02.23.432527.full AB - Since 1992 PredictProtein (https://predictprotein.org) is a one-stop online resource for protein sequence analysis with its main site hosted at the Luxembourg Centre for Systems Biomedicine (LCSB) and queried monthly by over 3,000 users in 2020. PredictProtein was the first Internet server for protein predictions. It pioneered combining evolutionary information and machine learning. Given a protein sequence as input, the server outputs multiple sequence alignments, predictions of protein structure in 1D and 2D (secondary structure, solvent accessibility, transmembrane segments, disordered regions, protein flexibility, and disulfide bridges) and predictions of protein function (functional effects of sequence variation or point mutations, Gene Ontology (GO) terms, subcellular localization, and protein-, RNA-, and DNA binding). PredictProtein’s infrastructure has moved to the LCSB increasing throughput; the use of MMseqs2 sequence search reduced runtime five-fold; user interface elements improved usability, and new prediction methods were added. PredictProtein recently included predictions from deep learning embeddings (GO and secondary structure) and a method for the prediction of proteins and residues binding DNA, RNA, or other proteins. PredictProtein.org aspires to provide reliable predictions to computational and experimental biologists alike. All scripts and methods are freely available for offline execution in high-throughput settings.Availability Freely accessible webserver PredictProtein.org; Source and docker images: github.com/rostlabCompeting Interest StatementThe authors have declared no competing interest.