ArticleProceedings of the National Academy of Sciences of the United States of America2011
Maps of protein structure space reveal a fundamental relationship between protein structure and function.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 38 papers.
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38 citing papers in PubMed.
- Contrastive learning unites sequence and structure in a global representation of protein space.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
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- Large protein databases reveal structural complementarity and functional locality.Nature communications · 2025Article
- Towards a comprehensive view of the pocketome universe-biological implications and algorithmic challenges.PLoS computational biology · 2025Article
- Pan-cancer structurome reveals overrepresentation of beta sandwiches and underrepresentation of alpha helical domains.Scientific reports · 2023Article
- Sequence-structure-function relationships in the microbial protein universe.Nature communications · 2023Article
- DomainMapper: Accurate domain structure annotation including those with non-contiguous topologies.Protein science : a publication of the Protein Society · 2022Article
- ProtGPT2 is a deep unsupervised language model for protein design.Nature communications · 2022Article
- Bridging Themes: Short Protein Segments Found in Different Architectures.Molecular biology and evolution · 2021Article
- Hinge-shift mechanism as a protein design principle for the evolution of β-lactamases from substrate promiscuity to specificity.Nature communications · 2021Article
- Local Bilayer Hydrophobicity Modulates Membrane Protein Stability.Journal of the American Chemical Society · 2021Article
- Expanded analyses of the functional correlations within structural classifications of glycoside hydrolases.Computational and structural biotechnology journal · 2021Article
- Identification and Analysis of Natural Building Blocks for Evolution-Guided Fragment-Based Protein Design.Journal of molecular biology · 2020Article
- Evaluating Autoencoder-Based Featurization and Supervised Learning for Protein Decoy Selection.Molecules (Basel, Switzerland) · 2020Article
- Posttranslational Modifications of Smurfs: Emerging Regulation in Cancer.Frontiers in oncology · 2020Review
- A Semi-Empirical Framework for Interpreting Traveling Wave Ion Mobility Arrival Time Distributions.Journal of the American Society for Mass Spectrometry · 2019Article
- A global map of the protein shape universe.PLoS computational biology · 2019Article
- Ligand Binding Site Structure Influences the Evolution of Protein Complex Function and Topology.Cell reports · 2018Article
- Collision induced unfolding of isolated proteins in the gas phase: past, present, and future.Current opinion in chemical biology · 2018Review
- Functional and Structural Diversity of Acyl-coA Binding Proteins in Oil Crops.Frontiers in genetics · 2018Review
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2 authors.
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Abstract
To study the protein structure-function relationship, we propose a method to efficiently create three-dimensional maps of structure space using a very large dataset of > 30,000 Structural Classification of Proteins (SCOP) domains. In our maps, each domain is represented by a point, and the distance between any two points approximates the structural distance between their corresponding domains. We use these maps to study the spatial distributions of properties of proteins, and in particular those of local vicinities in structure space such as structural density and functional diversity. These maps provide a unique broad view of protein space and thus reveal previously undescribed fundamental properties thereof. At the same time, the maps are consistent with previous knowledge (e.g., domains cluster by their SCOP class) and organize in a unified, coherent representation previous observation concerning specific protein folds. To investigate the function-structure relationship, we measure the functional diversity (using the Gene Ontology controlled vocabulary) in local structural vicinities. Our most striking finding is that functional diversity varies considerably across structure space: The space has a highly diverse region, and diversity abates when moving away from it. Interestingly, the domains in this region are mostly alpha/beta structures, which are known to be the most ancient proteins. We believe that our unique perspective of structure space will open previously undescribed ways of studying proteins, their evolution, and the relationship between their structure and function.
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