Definition and research guide
This page combines a MeSH definition, publication statistics and selected research abstracts. It is a starting point for reading the literature, not a medical textbook or a systematic evidence review.
Content available: 4 complete abstracts (531 words), 10 references. Full article text is not stored or reproduced here; follow the PMID, DOI or PMC links to read the original sources and their access terms.
Definition
The process in which substances, either endogenous or exogenous, bind to proteins, peptides, enzymes, protein precursors, or allied compounds. Specific protein-binding measures are often used as assays in diagnostic assessments.
Definition: NLM Medical Subject Headings (MeSH) scope note (Public domain (U.S. National Library of Medicine); attribution requested). View the MeSH record.
Also known as: Binding, Protein; Plasma Protein Binding Capacity.
Where it fits in the MeSH classification
- Broader topics
- Biochemical Phenomena; Metabolism
- See also
- Binding Sites; Carrier Proteins; Metalloproteins; Radioligand Assay; Thyroxine-Binding Proteins
Research landscape
PubMed indexes 314,021 records tagged with the MeSH heading “Protein Binding” (counts retrieved 2026-10-29). 39,759 of them (12.7%) were published from 2020 onward, and the busiest period so far is 2010-2019 with 106,840 records.
Reviews account for 19,615 records (6.2%) and meta-analyses for 54. Randomized controlled trials number 320 (0.1%) as a share of all records on the topic. Randomized trials make up only a small share of this literature, so much of what is known comes from laboratory, observational or descriptive work.
Show the data
| Period | Records |
|---|---|
| through 1999 | 79,371 |
| 2000-2009 | 88,051 |
| 2010-2019 | 106,840 |
| 2020 onward | 39,759 |
Publication-type chart data
| Type | Records | Share |
|---|---|---|
| Reviews | 19,615 | 6.2% |
| Meta-analyses | 54 | 0.0% |
| Randomized controlled trials | 320 | 0.1% |
Method: PubMed query "Protein Binding"[MeSH Terms] with publication-type and date filters, retrieved 2026-10-29.
Reading the evidence in molecular biology
Molecular biology establishes mechanisms through controlled experiments, often in simplified systems such as purified proteins, cultured cells or model organisms. Such work can show what is possible in a defined system, but whether a pathway matters in a whole organism or in human disease needs further evidence. Check the experimental system, whether findings were reproduced by independent groups, and whether the authors tested the mechanism directly or inferred it from correlation.
Evidence from open-access studies
These open-access studies come from PubMed’s best-match results for this heading (papers whose main topic it is), ranked here by citation count, with one recent addition. Each abstract is reproduced in full under its recorded open licence so that you can read the authors’ own words. They illustrate the literature; they are not a systematic summary of it. Citation counts measure attention, not reliability or clinical benefit.
| Study / authors | Year | Source label / design | Europe PMC citations | Licence / source |
|---|---|---|---|---|
| Geometric deep learning of protein-DNA binding specificity | 2024 | Research article Design not recorded in structured metadata | 61 | cc by PMID 39103447 · DOI · PMC11399107 |
| A specific phosphorylation-dependent conformational switch in SARS-CoV-2 nucleocapsid protein inhibits RNA binding | 2024 | Research article Design not recorded in structured metadata | 34 | cc by PMID 39093972 · DOI · PMC11296341 |
| The molecular dissection of TRIM25's RNA-binding mechanism provides key insights into its antiviral activity | 2024 | Research article Design not recorded in structured metadata | 32 | cc by PMID 39353916 · DOI · PMC11445558 |
| Label-Free and Immobilization-Free Protein-Binding Assays by Ultraviolet Transient Absorption Microscopy | 2026 | Research article Design not recorded in structured metadata | 0 | cc by PMID 41589616 · DOI · PMC13045408 |
Geometric deep learning of protein-DNA binding specificity [1]
Abstract reading summary — source excerpts
- Opening excerpt
- Predicting protein-DNA binding specificity is a challenging yet essential task for understanding gene regulation.
- Closing excerpt
- DeepPBS offers a foundation for machine-aided studies that advance our understanding of molecular interactions and guide experimental designs and synthetic biology.
- Interpretation limits
- Verbatim excerpts from the authors’ abstract; the closing excerpt may describe a finding, limitation or recommendation. Design, population, effect size and uncertainty have not been independently extracted or appraised. Read the complete abstract and linked paper before interpreting the findings.
Read complete abstract (150 words)
Predicting protein-DNA binding specificity is a challenging yet essential task for understanding gene regulation. Protein-DNA complexes usually exhibit binding to a selected DNA target site, whereas a protein binds, with varying degrees of binding specificity, to a wide range of DNA sequences. This information is not directly accessible in a single structure. Here, to access this information, we present Deep Predictor of Binding Specificity (DeepPBS), a geometric deep-learning model designed to predict binding specificity from protein-DNA structure. DeepPBS can be applied to experimental or predicted structures. Interpretable protein heavy atom importance scores for interface residues can be extracted. When aggregated at the protein residue level, these scores are validated through mutagenesis experiments. Applied to designed proteins targeting specific DNA sequences, DeepPBS was demonstrated to predict experimentally measured binding specificity. DeepPBS offers a foundation for machine-aided studies that advance our understanding of molecular interactions and guide experimental designs and synthetic biology.
Abstract reproduced from the open-access article under the recorded cc by licence; © the authors. PMID 39103447 · DOI · PMC11399107
A specific phosphorylation-dependent conformational switch in SARS-CoV-2 nucleocapsid protein inhibits RNA binding [2]
Abstract reading summary — source excerpts
- Opening excerpt
- The nucleocapsid protein of severe acute respiratory syndrome coronavirus 2 encapsidates the viral genome and is essential for viral function.
- Closing excerpt
- This study provides insight into the recruitment of specific host kinases to regulate viral function.
- Interpretation limits
- Verbatim excerpts from the authors’ abstract; the closing excerpt may describe a finding, limitation or recommendation. Design, population, effect size and uncertainty have not been independently extracted or appraised. Read the complete abstract and linked paper before interpreting the findings.
Read complete abstract (159 words)
The nucleocapsid protein of severe acute respiratory syndrome coronavirus 2 encapsidates the viral genome and is essential for viral function. The central disordered domain comprises a serine-arginine-rich (SR) region that is hyperphosphorylated in infected cells. This modification regulates function, although mechanistic details remain unknown. We use nuclear magnetic resonance to follow structural changes occurring during hyperphosphorylation by serine arginine protein kinase 1, glycogen synthase kinase 3, and casein kinase 1, that abolishes interaction with RNA. When eight approximately uniformly distributed sites have been phosphorylated, the SR domain binds the same interface as single-stranded RNA, resulting in complete inhibition of RNA binding. Phosphorylation by protein kinase A does not prevent RNA binding, indicating that the pattern resulting from physiologically relevant kinases is specific for inhibition. Long-range contacts between the RNA binding, linker, and dimerization domains are abrogated, phenomena possibly related to genome packaging and unpackaging. This study provides insight into the recruitment of specific host kinases to regulate viral function.
Abstract reproduced from the open-access article under the recorded cc by licence; © the authors. PMID 39093972 · DOI · PMC11296341
The molecular dissection of TRIM25's RNA-binding mechanism provides key insights into its antiviral activity [3]
Abstract reading summary — source excerpts
- Opening excerpt
- TRIM25 is an RNA-binding ubiquitin E3 ligase with central but poorly understood roles in the innate immune response to RNA viruses.
- Closing excerpt
- Using iCLIP2 in virus-infected and uninfected cells, we identified TRIM25's RNA sequence and structure specificity, that it binds specifically to viral RNA, and that the interaction with RNA is critical for its antiviral activity.
- Interpretation limits
- Verbatim excerpts from the authors’ abstract; the closing excerpt may describe a finding, limitation or recommendation. Design, population, effect size and uncertainty have not been independently extracted or appraised. Read the complete abstract and linked paper before interpreting the findings.
Read complete abstract (93 words)
TRIM25 is an RNA-binding ubiquitin E3 ligase with central but poorly understood roles in the innate immune response to RNA viruses. The link between TRIM25's RNA binding and its role in innate immunity has not been established. Thus, we utilized a multitude of biophysical techniques to identify key RNA-binding residues of TRIM25 and developed an RNA-binding deficient mutant (TRIM25-m9). Using iCLIP2 in virus-infected and uninfected cells, we identified TRIM25's RNA sequence and structure specificity, that it binds specifically to viral RNA, and that the interaction with RNA is critical for its antiviral activity.
Abstract reproduced from the open-access article under the recorded cc by licence; © the authors. PMID 39353916 · DOI · PMC11445558
Label-Free and Immobilization-Free Protein-Binding Assays by Ultraviolet Transient Absorption Microscopy [4]
Abstract reading summary — source excerpts
- Opening excerpt
- Protein-ligand interactions are central to understanding biological mechanisms and drug discovery, yet conventional assays often rely on labeling or immobilization that can alter natural binding.
- Closing excerpt
- UV-TAM thus provides a robust, calibration-free platform for studying protein interactions in solution, with significant potential for biochemical research and high-throughput drug discovery.
- Interpretation limits
- Verbatim excerpts from the authors’ abstract; the closing excerpt may describe a finding, limitation or recommendation. Design, population, effect size and uncertainty have not been independently extracted or appraised. Read the complete abstract and linked paper before interpreting the findings.
Read complete abstract (129 words)
Protein-ligand interactions are central to understanding biological mechanisms and drug discovery, yet conventional assays often rely on labeling or immobilization that can alter natural binding. Here, we introduce ultraviolet transient absorption microscopy (UV-TAM), which directly detects binding through ligand-induced changes in the excited-state dynamics of tryptophan residues. Using a femtosecond deep-UV pump and a near-UV probe, UV-TAM enables label-free, in-solution measurements with only microliter sample volumes. We demonstrate its capability using plasma proteins-bovine serum albumin and hemoglobin-with alkaloid ligands, berberine and palmatine. Binding events are clearly identified through time-resolved spectral changes. Quantitative analysis of hemoglobin-alkaloid interactions yields dissociation constants in close agreement with isothermal titration calorimetry. UV-TAM thus provides a robust, calibration-free platform for studying protein interactions in solution, with significant potential for biochemical research and high-throughput drug discovery.
Abstract reproduced from the open-access article under the recorded cc by licence; © the authors. PMID 41589616 · DOI · PMC13045408
Key reviews and meta-analyses
The most cited review-type papers among PubMed’s best-match results for this heading, listed with bibliographic details only. Follow the links for the full text and access terms.
- Research article Principles of protein-protein interactions [5]
- Research article Coupling of folding and binding for unstructured proteins [6]
- Research article Calculation of protein-ligand binding affinities [7]
- Research article The structure of protein-protein recognition sites [8]
- Research article Unraveling hot spots in binding interfaces: progress and challenges [9]
- Research article Protein-ligand docking: current status and future challenges [10]
References
- Mitra R, Li J, Sagendorf JM, Jiang Y, Cohen AS, Chiu TP, et al.. Geometric deep learning of protein-DNA binding specificity. . 2024. PMID 39103447 · DOI · PMC11399107
- Botova M, Camacho-Zarco AR, Tognetti J, Bessa LM, Guseva S, Mikkola E, et al.. A specific phosphorylation-dependent conformational switch in SARS-CoV-2 nucleocapsid protein inhibits RNA binding. . 2024. PMID 39093972 · DOI · PMC11296341
- Álvarez L, Haubrich K, Iselin L, Gillioz L, Ruscica V, Lapouge K, et al.. The molecular dissection of TRIM25's RNA-binding mechanism provides key insights into its antiviral activity. . 2024. PMID 39353916 · DOI · PMC11445558
- Shen J, Wang Q, Wu F, Gao Y, Lan L, Wang P. Label-Free and Immobilization-Free Protein-Binding Assays by Ultraviolet Transient Absorption Microscopy. . 2026. PMID 41589616 · DOI · PMC13045408
- Jones S, Thornton JM. Principles of protein-protein interactions. Proc Natl Acad Sci U S A. 1996. PMID 8552589 · DOI · PMC40170
- Dyson HJ, Wright PE. Coupling of folding and binding for unstructured proteins. Curr Opin Struct Biol. 2002. PMID 11839490 · DOI
- Gilson MK, Zhou HX. Calculation of protein-ligand binding affinities. Annu Rev Biophys Biomol Struct. 2007. PMID 17201676 · DOI
- Janin J, Chothia C. The structure of protein-protein recognition sites. J Biol Chem. 1990. PMID 2204619 · DOI
- DeLano WL. Unraveling hot spots in binding interfaces: progress and challenges. Curr Opin Struct Biol. 2002. PMID 11839484 · DOI
- Sousa SF, Fernandes PA, Ramos MJ. Protein-ligand docking: current status and future challenges. Proteins. 2006. PMID 16862531 · DOI
About this article
- Sources
- NLM Medical Subject Headings (definition, synonyms); NCBI PubMed (counts, identifiers); Europe PMC (open-access abstracts and citation counts).
- Verification
- Every reference was resolved against PubMed on 2026-10-31; title, year and DOI matched.
- Review state
- automated source verified; no human expert review has been recorded yet.
- Version
- 1, last updated 2026-10-29.
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Evidence strength
EvidenceHelix's computed view of the study designs behind this topic: how common meta-analyses, randomized trials and reviews are, how recent the literature is, and a plain-language reading. It describes the design mix of the literature. It is not a quality appraisal of any study, and it is not medical advice.