ArticleProceedings of the National Academy of Sciences of the United States of America2012
The distribution of ligand-binding pockets around protein-protein interfaces suggests a general mechanism for pocket formation.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 51 papers.
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Who cites it
51 citing papers in PubMed.
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- Entabolons: How Metabolites Modify the Biochemical Function of Proteins and Cause the Correlated Behavior of Proteins in Pathways.Journal of chemical information and modeling · 2025Review
- Quantitative Characterization of the Impact of Protein-Protein Interactions on Ligand-Protein Binding: A Multi-Chain Dynamics Perturbation Analysis Method.International journal of molecular sciences · 2024Article
- Binding and sensing diverse small molecules using shape-complementary pseudocycles.Science (New York, N.Y.) · 2024Article
- De novo design of diverse small molecule binders and sensors using Shape Complementary Pseudocycles.bioRxiv : the preprint server for biology · 2023Article
- Prediction of Protein Ion-Ligand Binding Sites with ELECTRA.Molecules (Basel, Switzerland) · 2023Article
- Comprehensive chemo-profiling of coumarins enriched extract derived fromSaudi pharmaceutical journal : SPJ : the official publication of the Saudi Pharmaceutical Society · 2023Article
- Structural insights into the interaction of three Y-shaped ligands with PI3Kα.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- What Makes a Good Protein-Protein Interaction Stabilizer: Analysis and Application of the Dual-Binding Mechanism.ACS central science · 2023Article
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- Prediction of the tetramer protein complex interaction based on CNN and SVM.Frontiers in genetics · 2023Article
- Implications of the Essential Role of Small Molecule Ligand Binding Pockets in Protein-Protein Interactions.The journal of physical chemistry. B · 2022Article
- Catalysis and Electron Transfer inChemical reviews · 2022Review
- Mitigating cold-start problems in drug-target affinity prediction with interaction knowledge transferring.Briefings in bioinformatics · 2022Article
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2 authors.
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Abstract
Protein-protein and protein-ligand interactions are ubiquitous in a biological cell. Here, we report a comprehensive study of the distribution of protein-ligand interaction sites, namely ligand-binding pockets, around protein-protein interfaces where protein-protein interactions occur. We inspected a representative set of 1,611 representative protein-protein complexes and identified pockets with a potential for binding small molecule ligands. The majority of these pockets are within a 6 Å distance from protein interfaces. Accordingly, in about half of ligand-bound protein-protein complexes, amino acids from both sides of a protein interface are involved in direct contacts with at least one ligand. Statistically, ligands are closer to a protein-protein interface than a random surface patch of the same solvent accessible surface area. Similar results are obtained in an analysis of the ligand distribution around domain-domain interfaces of 1,416 nonredundant, two-domain protein structures. Furthermore, comparable sized pockets as observed in experimental structures are present in artificially generated protein complexes, suggesting that the prominent appearance of pockets around protein interfaces is mainly a structural consequence of protein packing and thus, is an intrinsic geometric feature of protein structure. Nature may take advantage of such a structural feature by selecting and further optimizing for biological function. We propose that packing nearby protein-protein or domain-domain interfaces is a major route to the formation of ligand-binding pockets.
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