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      PredictProtein - Predicting Protein Structure and Function for 29 Years

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          Abstract

          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 (apparently without lowering performance of prediction methods); 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.

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          Graphical Abstract

          Queried by protein sequences, PredictProtein generates multiple sequence alignments and predicts aspects of protein function and structure through database lookups, homology-based inference, machine learning and artificial intelligence.

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          Most cited references66

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          Basic local alignment search tool.

          A new approach to rapid sequence comparison, basic local alignment search tool (BLAST), directly approximates alignments that optimize a measure of local similarity, the maximal segment pair (MSP) score. Recent mathematical results on the stochastic properties of MSP scores allow an analysis of the performance of this method as well as the statistical significance of alignments it generates. The basic algorithm is simple and robust; it can be implemented in a number of ways and applied in a variety of contexts including straightforward DNA and protein sequence database searches, motif searches, gene identification searches, and in the analysis of multiple regions of similarity in long DNA sequences. In addition to its flexibility and tractability to mathematical analysis, BLAST is an order of magnitude faster than existing sequence comparison tools of comparable sensitivity.
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            Gapped BLAST and PSI-BLAST: a new generation of protein database search programs.

            S Altschul (1997)
            The BLAST programs are widely used tools for searching protein and DNA databases for sequence similarities. For protein comparisons, a variety of definitional, algorithmic and statistical refinements described here permits the execution time of the BLAST programs to be decreased substantially while enhancing their sensitivity to weak similarities. A new criterion for triggering the extension of word hits, combined with a new heuristic for generating gapped alignments, yields a gapped BLAST program that runs at approximately three times the speed of the original. In addition, a method is introduced for automatically combining statistically significant alignments produced by BLAST into a position-specific score matrix, and searching the database using this matrix. The resulting Position-Specific Iterated BLAST (PSI-BLAST) program runs at approximately the same speed per iteration as gapped BLAST, but in many cases is much more sensitive to weak but biologically relevant sequence similarities. PSI-BLAST is used to uncover several new and interesting members of the BRCT superfamily.
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              The Protein Data Bank.

              The Protein Data Bank (PDB; http://www.rcsb.org/pdb/ ) is the single worldwide archive of structural data of biological macromolecules. This paper describes the goals of the PDB, the systems in place for data deposition and access, how to obtain further information, and near-term plans for the future development of the resource.
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                Author and article information

                Contributors
                Journal
                Nucleic Acids Res
                Nucleic Acids Res
                nar
                Nucleic Acids Research
                Oxford University Press
                0305-1048
                1362-4962
                02 July 2021
                17 May 2021
                17 May 2021
                : 49
                : W1
                : W535-W540
                Affiliations
                TUM (Technical University of Munich) Department of Informatics , Bioinformatics & Computational Biology - i12, Boltzmannstr 3, 85748 Garching/Munich, Germany
                TUM Graduate School CeDoSIA , Boltzmannstr 11, 85748 Garching, Germany
                TUM (Technical University of Munich) Department of Informatics , Bioinformatics & Computational Biology - i12, Boltzmannstr 3, 85748 Garching/Munich, Germany
                TUM Graduate School CeDoSIA , Boltzmannstr 11, 85748 Garching, Germany
                TUM (Technical University of Munich) Department of Informatics , Bioinformatics & Computational Biology - i12, Boltzmannstr 3, 85748 Garching/Munich, Germany
                Luxembourg Centre For Systems Biomedicine (LCSB), University of Luxembourg , Campus Belval, House of Biomedicine II, 6 avenue du Swing, L-4367 Belvaux, Luxembourg
                ELIXIR Luxembourg (ELIXIR-LU) Node, University of Luxembourg , Campus Belval, House of Biomedicine II, 6 avenue du Swing, L-4367 Belvaux, Luxembourg
                TUM (Technical University of Munich) Department of Informatics , Bioinformatics & Computational Biology - i12, Boltzmannstr 3, 85748 Garching/Munich, Germany
                TUM Graduate School CeDoSIA , Boltzmannstr 11, 85748 Garching, Germany
                TUM (Technical University of Munich) Department of Informatics , Bioinformatics & Computational Biology - i12, Boltzmannstr 3, 85748 Garching/Munich, Germany
                TUM Graduate School CeDoSIA , Boltzmannstr 11, 85748 Garching, Germany
                TUM (Technical University of Munich) Department of Informatics , Bioinformatics & Computational Biology - i12, Boltzmannstr 3, 85748 Garching/Munich, Germany
                TUM (Technical University of Munich) Department of Informatics , Bioinformatics & Computational Biology - i12, Boltzmannstr 3, 85748 Garching/Munich, Germany
                Department of Otolaryngology Head & Neck Surgery, The Ninth People's Hospital & Ear Institute, School of Medicine & Shanghai Key Laboratory of Translational Medicine on Ear and Nose Diseases, Shanghai Jiao Tong University , Shanghai, China
                TUM (Technical University of Munich) Department of Informatics , Bioinformatics & Computational Biology - i12, Boltzmannstr 3, 85748 Garching/Munich, Germany
                TUM (Technical University of Munich) Department of Informatics , Bioinformatics & Computational Biology - i12, Boltzmannstr 3, 85748 Garching/Munich, Germany
                Department of Molecular Biology, Max Planck Institute for Developmental Biology , Tübingen, Germany
                The Shmunis School of Biomedicine and Cancer Research, George S. Wise Faculty of Life Sciences, Tel Aviv University , 69978 Tel Aviv, Israel
                Department of Biochemistry & Molecular Biology, George S. Wise Faculty of Life Sciences, Tel Aviv University , 69978 Tel Aviv, Israel
                Department of Biochemistry and Microbiology, Rutgers University , New Brunswick, NJ 08901, USA
                TUM (Technical University of Munich) Department of Informatics , Bioinformatics & Computational Biology - i12, Boltzmannstr 3, 85748 Garching/Munich, Germany
                Roche Polska Sp. z o.o. , Domaniewska 39B, 02–672 Warsaw, Poland
                Garvan Institute of Medical Research , Sydney, Australia
                Department of Data Sciences, Dana-Farber Cancer Institute , Boston, MA 02215, USA
                Department of Cell Biology, Harvard Medical School , Boston, MA 02215, USA
                Broad Institute of MIT and Harvard , Boston, MA 02142, USA
                TUM (Technical University of Munich) Department of Informatics , Bioinformatics & Computational Biology - i12, Boltzmannstr 3, 85748 Garching/Munich, Germany
                HSWT (Hochschule Weihenstephan Triesdorf | University of Applied Sciences), Department of Bioengineering Sciences , Am Hofgarten 10, 85354 Freising, Germany
                Department of Pharmacological Sciences , Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA
                BIPS, Poblacion Baco , Mindoro, Philippines
                Quantitative and Computational Biology, Max Planck Institute for Biophysical Chemistry , Göttingen, Germany
                Luxembourg Centre For Systems Biomedicine (LCSB), University of Luxembourg , Campus Belval, House of Biomedicine II, 6 avenue du Swing, L-4367 Belvaux, Luxembourg
                Luxembourg Centre For Systems Biomedicine (LCSB), University of Luxembourg , Campus Belval, House of Biomedicine II, 6 avenue du Swing, L-4367 Belvaux, Luxembourg
                ELIXIR Luxembourg (ELIXIR-LU) Node, University of Luxembourg , Campus Belval, House of Biomedicine II, 6 avenue du Swing, L-4367 Belvaux, Luxembourg
                Luxembourg Centre For Systems Biomedicine (LCSB), University of Luxembourg , Campus Belval, House of Biomedicine II, 6 avenue du Swing, L-4367 Belvaux, Luxembourg
                ELIXIR Luxembourg (ELIXIR-LU) Node, University of Luxembourg , Campus Belval, House of Biomedicine II, 6 avenue du Swing, L-4367 Belvaux, Luxembourg
                Luxembourg Centre For Systems Biomedicine (LCSB), University of Luxembourg , Campus Belval, House of Biomedicine II, 6 avenue du Swing, L-4367 Belvaux, Luxembourg
                ELIXIR Luxembourg (ELIXIR-LU) Node, University of Luxembourg , Campus Belval, House of Biomedicine II, 6 avenue du Swing, L-4367 Belvaux, Luxembourg
                School of Biological Sciences, Seoul National University , Seoul, South Korea
                Artificial Intelligence Institute, Seoul National University , Seoul, South Korea
                Luxembourg Centre For Systems Biomedicine (LCSB), University of Luxembourg , Campus Belval, House of Biomedicine II, 6 avenue du Swing, L-4367 Belvaux, Luxembourg
                ELIXIR Luxembourg (ELIXIR-LU) Node, University of Luxembourg , Campus Belval, House of Biomedicine II, 6 avenue du Swing, L-4367 Belvaux, Luxembourg
                TUM (Technical University of Munich) Department of Informatics , Bioinformatics & Computational Biology - i12, Boltzmannstr 3, 85748 Garching/Munich, Germany
                Institute for Advanced Study (TUM-IAS) , Lichtenbergstr. 2a, 85748 Garching/Munich, Germany
                TUM School of Life Sciences Weihenstephan (WZW) , Alte Akademie 8, Freising, Germany
                Author notes
                To whom correspondence should be addressed. Tel: +49 289 17 811; Email: christian.dallago@ 123456tum.de
                Correspondence may also be addressed to Burkhard Rost. Email: assistant@ 123456rostlab.org

                The authors wish it to be known that, in their opinion, the first four authors should be regarded as joint First Authors.

                Author information
                https://orcid.org/0000-0001-6103-3306
                https://orcid.org/0000-0003-4650-6181
                https://orcid.org/0000-0002-6532-5880
                https://orcid.org/0000-0003-1790-8536
                https://orcid.org/0000-0002-8351-0844
                https://orcid.org/0000-0001-8637-6719
                https://orcid.org/0000-0002-8991-6810
                https://orcid.org/0000-0002-8278-1618
                Article
                gkab354
                10.1093/nar/gkab354
                8265159
                33999203
                23f53e9a-fc67-4a31-927f-1810a3650898
                © The Author(s) 2021. Published by Oxford University Press on behalf of Nucleic Acids Research.

                This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( http://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 10 May 2021
                : 06 April 2021
                : 23 February 2021
                Page count
                Pages: 6
                Funding
                Funded by: Competence Network for Scientific High Performance Computing in Bavaria;
                Award ID: KONWIHR-III BG.DAF
                Funded by: Deutsche Forschungsgemeinschaft, DOI 10.13039/501100001659;
                Award ID: RO 1320/4-1
                Funded by: Bundesministerium für Bildung und Forschung, DOI 10.13039/501100002347;
                Award ID: 031L0168
                Funded by: BMBF, DOI 10.13039/501100002347;
                Award ID: 01IS17049
                Funded by: Horizon 2020 Framework Programme, DOI 10.13039/100010661;
                Award ID: 685778
                Funded by: National Research Foundation of Korea, DOI 10.13039/501100003725;
                Award ID: 2019R1A6A1A10073437
                Award ID: NRF-2020M3A9G7103933
                Funded by: Seoul National University, DOI 10.13039/501100002551;
                Funded by: Israeli Science Foundation;
                Award ID: 450/16
                Funded by: Tel Aviv University, DOI 10.13039/501100004375;
                Funded by: Alexander von Humboldt Foundation, DOI 10.13039/100005156;
                Funded by: Technical University of Munich, DOI 10.13039/501100005713;
                Categories
                AcademicSubjects/SCI00010
                Web Server Issue

                Genetics
                Genetics

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