ArticleNature2015
Exploring the repeat protein universe through computational protein design.
Article in Nature, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 150 papers.
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Who cites it
150 citing papers in PubMed.
- HURDLER: a cloning method to overcome length limits in designed repeat proteins.Nucleic acids research · 2026Article
- Near-Infrared Fluorescence Imaging and Photothermal Therapy of Tumors Using a Targeted Helical Protein Scaffold.ACS applied bio materials · 2026Article
- Distinct repeat architecture landscapes in the proteomes of protozoan parasites.NAR genomics and bioinformatics · 2026Article
- De novo design of miniproteins targeting GPCRs.Nature · 2026Article
- Highly dynamic assemblies of glycolytic enzymes by quinary determinants.Nature communications · 2026Article
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- Using experimental results of protein design to guide biomolecular energy-function development.PLoS computational biology · 2026Article
- Protein folding stability estimation with explicit consideration of unfolded states.Nature communications · 2026Article
- Site-specific labelling of native peptides and proteins: chemical and enzymatic strategies.Beilstein journal of organic chemistry · 2026Review
- Designability of α-Helical Protein Filaments.Sub-cellular biochemistry · 2026Review
- Designing novel solenoid proteins with in silico evolution.Communications chemistry · 2025Article
- Bottom-up design of CaNature · 2025Article
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- De novo design of metal-oxide templating proteins.bioRxiv : the preprint server for biology · 2025Article
- Geometric Tuning of Cytokine Receptor Association Modulates Synthetic Agonist Signaling.bioRxiv : the preprint server for biology · 2025Article
- Efficient protein structure generation with sparse denoising models.Nature machine intelligence · 2025Article
- Information theory optimization of signals from small-angle scattering measurements.Biophysical journal · 2025Article
- Multistate and functional protein design using RoseTTAFold sequence space diffusion.Nature biotechnology · 2025Article
- GeomeTRe: accurate calculation of geometrical descriptors of tandem repeat proteins.Bioinformatics (Oxford, England) · 2025Article
90 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
9 authors.
Funding
Abstract
A central question in protein evolution is the extent to which naturally occurring proteins sample the space of folded structures accessible to the polypeptide chain. Repeat proteins composed of multiple tandem copies of a modular structure unit are widespread in nature and have critical roles in molecular recognition, signalling, and other essential biological processes. Naturally occurring repeat proteins have been re-engineered for molecular recognition and modular scaffolding applications. Here we use computational protein design to investigate the space of folded structures that can be generated by tandem repeating a simple helix-loop-helix-loop structural motif. Eighty-three designs with sequences unrelated to known repeat proteins were experimentally characterized. Of these, 53 are monomeric and stable at 95 °C, and 43 have solution X-ray scattering spectra consistent with the design models. Crystal structures of 15 designs spanning a broad range of curvatures are in close agreement with the design models with root mean square deviations ranging from 0.7 to 2.5 Å. Our results show that existing repeat proteins occupy only a small fraction of the possible repeat protein sequence and structure space and that it is possible to design novel repeat proteins with precisely specified geometries, opening up a wide array of new possibilities for biomolecular engineering.
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