ArticleProceedings of the National Academy of Sciences of the United States of America2014
Global view of the protein universe.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 49 papers.
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Who cites it
49 citing papers in PubMed, 80 citations in OpenAlex.
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- TEDLH: domain HMMs for sensitive detection of remote homologues.Bioinformatics (Oxford, England) · 2026Article
- Exploring the structural lexicon of the Proteome via Metric Geometry.PLoS computational biology · 2026Article
- The Borderlands of Foldability: Lessons from Simplified Proteins.Trends in chemistry · 2026Article
- Whole-genome combinatorial gene fusions generate novel genes for advanced microbial trait development.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- The Analysis ofCurrent issues in molecular biology · 2025Article
- Piecing Together the History of Protein Folds From a Fragmented Evolutionary Record.Genome biology and evolution · 2025Article
- Impact of local unfolding fluctuations on the evolution of regional sequence preferences in proteins.Protein science : a publication of the Protein Society · 2025Article
- Fast protein structure searching using structure graph embeddings.Bioinformatics advances · 2025Article
- On Protein Loops, Prior Molecular States and Common Ancestors of Life.Journal of molecular evolution · 2024Review
- Reused Protein Segments Linked to Functional Dynamics.Molecular biology and evolution · 2024Article
- Article
- Tracing the birth of structural domains from loops during protein evolution.Scientific reports · 2023Article
- Classification of domains in predicted structures of the human proteome.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- A review of visualisations of protein fold networks and their relationship with sequence and function.Biological reviews of the Cambridge Philosophical Society · 2023Review
- Evolutionary Conserved Short Linear Motifs Provide Insights into the Cellular Response to Stress.Antioxidants (Basel, Switzerland) · 2022Article
- Creative destruction: New protein folds from old.Proceedings of the National Academy of Sciences of the United States of America · 2022Article
- Similar protein segments shared between domains of different evolutionary lineages.Protein science : a publication of the Protein Society · 2022Article
- ProtGPT2 is a deep unsupervised language model for protein design.Nature communications · 2022Article
Corrections and comments
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Authors and funding
3 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
To explore protein space from a global perspective, we consider 9,710 SCOP (Structural Classification of Proteins) domains with up to 70% sequence identity and present all similarities among them as networks: In the "domain network," nodes represent domains, and edges connect domains that share "motifs," i.e., significantly sized segments of similar sequence and structure. We explore the dependence of the network on the thresholds that define the evolutionary relatedness of the domains. At excessively strict thresholds the network falls apart completely; for very lax thresholds, there are network paths between virtually all domains. Interestingly, at intermediate thresholds the network constitutes two regions that can be described as "continuous" versus "discrete." The continuous region comprises a large connected component, dominated by domains with alternating alpha and beta elements, and the discrete region includes the rest of the domains in isolated islands, each generally corresponding to a fold. We also construct the "motif network," in which nodes represent recurring motifs, and edges connect motifs that appear in the same domain. This network also features a large and highly connected component of motifs that originate from domains with alternating alpha/beta elements (and some all-alpha domains), and smaller isolated islands. Indeed, the motif network suggests that nature reuses such motifs extensively. The networks suggest evolutionary paths between domains and give hints about protein evolution and the underlying biophysics. They provide natural means of organizing protein space, and could be useful for the development of strategies for protein search and design.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.