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We are analyzing https://www.nature.com/articles/s41598-021-03431-4.

Title:
Protein embeddings and deep learning predict binding residues for various ligand classes | Scientific Reports
Description:
One important aspect of protein function is the binding of proteins to ligands, including small molecules, metal ions, and macromolecules such as DNA or RNA. Despite decades of experimental progress many binding sites remain obscure. Here, we proposed bindEmbed21, a method predicting whether a protein residue binds to metal ions, nucleic acids, or small molecules. The Artificial Intelligence (AI)-based method exclusively uses embeddings from the Transformer-based protein Language Model (pLM) ProtT5 as input. Using only single sequences without creating multiple sequence alignments (MSAs), bindEmbed21DL outperformed MSA-based predictions. Combination with homology-based inference increased performance to F1 = 48 ± 3% (95% CI) and MCC = 0.46 ± 0.04 when merging all three ligand classes into one. All results were confirmed by three independent data sets. Focusing on very reliably predicted residues could complement experimental evidence: For the 25% most strongly predicted binding residues, at least 73% were correctly predicted even when ignoring the problem of missing experimental annotations. The new method bindEmbed21 is fast, simple, and broadly applicable—neither using structure nor MSAs. Thereby, it found binding residues in over 42% of all human proteins not otherwise implied in binding and predicted about 6% of all residues as binding to metal ions, nucleic acids, or small molecules.
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Keywords {🔍}

binding, proteins, residues, protein, annotations, predicted, predictions, article, pubmed, bindembeddl, prediction, google, scholar, fig, supplementary, cas, ligand, data, method, nucleic, sequence, table, performance, set, small, precision, methods, hbi, residue, acids, embeddings, classes, learning, experimental, metal, central, structure, reliable, recall, predict, molecules, nonbinding, probability, information, rost, biolip, ions, bind, function, nature,

Topics {✒️}

$$mcc=\frac{tp\cdot tn-fp\cdot fn}{\sqrt{ nature portfolio privacy policy nature https advertising research nature 468 nature precision=\frac{tn}{tn+ff} social media recall=\frac{tn}{tn+fp} $$precision=\frac{tp}{tp+fp} $$recall=\frac{tp}{tp+fn} embedding-based msa-free bindembed21dl tools reprints profile-based string kernels pipenn-emb ensemble net author information authors reliability index discussion embedding-based predictions semi-manually curated database cross-entropy loss function protein–protein interaction information motif-based profile-kernel58 f1=2\cdot \frac{negative protein language model ai/deep learning architecture protein–dna interface database homology-based inference sets combined homology-based inference challenge machine learning quantitative high-throughput proteomics protein-function prediction methods predictprotein—predicting protein structure outperformed msa-based predictions permissions original author dna-binding protein hmf-2 author correspondence msa-derived input features low-resolution structures 3q1q prona2020 predicts protein–dna msa-based method bindpredictml17 natural language processing full size image expert-crafted features protein–protein binding proteins typical cross-validation split machine learning method

Questions {❓}

  • Although apparently blatantly underestimating precision, this crude simplification was needed to avoid over-prediction: methods only considering “what fraction of the experimental annotations is predicted?
  • Common sequence variants affect molecular function more than rare variants?
  • For instance, ProNA202019 focuses on predicting protein-, DNA-, or RNA-binding, both on the per-protein (does protein bind DNA or not?
  • What’s in a name?

Schema {🗺️}

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      name:TUM Graduate School, Center of Doctoral Studies in Informatics and Its Applications (CeDoSIA), Garching, Germany
      name:Department of Informatics, Bioinformatics and Computational Biology, I12, TUM (Technical University of Munich), Garching/Munich, Germany
      name:Institute for Advanced Study (TUM-IAS), Munich, Germany
      name:TUM School of Life Sciences Weihenstephan (TUM-WZW), Freising, Germany
      name:Department of Biochemistry and Molecular Biophysics, Columbia University, New York, USA

External Links {🔗}(262)

Analytics and Tracking {📊}

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Libraries {📚}

  • Prism.js
  • Zoom.js

Emails and Hosting {✉️}

Mail Servers:

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Name Servers:

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  • pdns6.ultradns.co.uk

CDN Services {📦}

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