ArticleProceedings of the National Academy of Sciences of the United States of America2010
Structural space of protein-protein interfaces is degenerate, close to complete, and highly connected.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 75 papers.
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Who cites it
75 citing papers in PubMed.
- Black-box data: a new paradigm for biomedicine in the AI era.Chemical science · 2026Review
- Article
- High-accuracy protein complex structure modeling based on sequence-derived structure complementarity.Nature communications · 2025Article
- DiPPI: A Curated Data Set for Drug-like Molecules in Protein-Protein Interfaces.Journal of chemical information and modeling · 2024Article
- Assessing the functional impact of protein binding site definition.Protein science : a publication of the Protein Society · 2024Article
- ARCTIC-3D: automatic retrieval and clustering of interfaces in complexes from 3D structural information.Communications biology · 2024Article
- Machine Learning-Guided Protein Engineering.ACS catalysis · 2023Review
- Designing Cyclic-Constrained Peptides to Inhibit Human Phosphoglycerate Dehydrogenase.Molecules (Basel, Switzerland) · 2023Article
- Implications of the Essential Role of Small Molecule Ligand Binding Pockets in Protein-Protein Interactions.The journal of physical chemistry. B · 2022Article
- Promiscuity mapping of the S100 protein family using a high-throughput holdup assay.Scientific reports · 2022Article
- AF2Complex predicts direct physical interactions in multimeric proteins with deep learning.Nature communications · 2022Article
- AlphaFold 2: Why It Works and Its Implications for Understanding the Relationships of Protein Sequence, Structure, and Function.Journal of chemical information and modeling · 2021Article
- Differentiable biology: using deep learning for biophysics-based and data-driven modeling of molecular mechanisms.Nature methods · 2021Review
- A fragment-based protein interface design algorithm for symmetric assemblies.Protein engineering, design & selection : PEDS · 2021Article
- Geometrical and electro-static determinants of protein-protein interactions.Bioinformation · 2021Article
- Bacteria use structural imperfect mimicry to hijack the host interactome.PLoS computational biology · 2020Article
- Repositioned Drugs for Chagas Disease Unveiled via Structure-Based Drug Repositioning.International journal of molecular sciences · 2020Article
- Uncovering the basis of protein-protein interaction specificity with a combinatorially complete library.eLife · 2020Article
- Proteomimetic surface fragments distinguish targets by function.Chemical science · 2020Article
- Integrating ab initio and template-based algorithms for protein-protein complex structure prediction.Bioinformatics (Oxford, England) · 2020Article
15 more citing papers are in PubMed but not listed here.
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2 authors.
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Abstract
At the heart of protein-protein interactions are protein-protein interfaces where the direct physical interactions occur. By developing and applying an efficient structural alignment method, we study the structural similarity of representative protein-protein interfaces involving interactions between dimers. Even without structural similarity between individual monomers that form dimeric complexes, ∼90% of native interfaces have a close structural neighbor with similar backbone C(α) geometry and interfacial contact pattern. About 80% of the interfaces form a dense network, where any two interfaces are structurally related using a transitive set of at most seven intermediate interfaces. The degeneracy of interface space is largely due to the packing of compact, hydrogen-bonded secondary structure elements. This packing generates relatively flat interacting surfaces whose geometries are highly degenerate. Comparative study of artificial and native interfaces argues that the library of protein interfaces is close to complete and comprised of roughly 1,000 distinct interface types. In contrast, the number of possible quaternary structures of dimers is estimated to be about 10(4) times larger; thus, an experimentally determined database of all representative quaternary structures is not likely in the near future. Nevertheless, one could in principle exploit the completeness of protein interfaces to predict most dimeric quaternary structures. Finally, our results provide a structural explanation for the prevalence of promiscuous protein interactions. By side-chain packing adjustments, we illustrate how multiprotein specificity can be attained at a promiscuous interface.
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