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 (680 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 parts of a macromolecule that directly participate in its specific combination with another molecule.
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: Site, Binding; Sites, Binding; Binding Site; Combining Site; Combining Sites; Site, Combining; Sites, Combining.
Where it fits in the MeSH classification
- Broader topics
- Molecular Structure
- Narrower topics
- Allosteric Site; Bay-Region, Polycyclic Aromatic Hydrocarbon; Binding Sites, Antibody; Binding, Competitive; Catalytic Domain
- See also
- Protein Binding; Receptors, Cell Surface
Research landscape
PubMed indexes 335,792 records tagged with the MeSH heading “Binding Sites” (counts retrieved 2026-10-29). 26,890 of them (8.0%) were published from 2020 onward, and the busiest period so far is through 1999 with 142,867 records.
Reviews account for 18,037 records (5.4%) and meta-analyses for 66. Randomized controlled trials number 108 (0.0%) 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 | 142,867 |
| 2000-2009 | 89,682 |
| 2010-2019 | 76,353 |
| 2020 onward | 26,890 |
Publication-type chart data
| Type | Records | Share |
|---|---|---|
| Reviews | 18,037 | 5.4% |
| Meta-analyses | 66 | 0.0% |
| Randomized controlled trials | 108 | 0.0% |
Method: PubMed query "Binding Sites"[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 |
|---|---|---|---|---|
| Fragment binding to the Nsp3 macrodomain of SARS-CoV-2 identified through crystallographic screening and computational docking | 2021 | Research article Design not recorded in structured metadata | 179 | cc by PMID 33853786 · DOI · PMC8046379 |
| The energetic and allosteric landscape for KRAS inhibition | 2024 | Research article Design not recorded in structured metadata | 168 | cc by PMID 38109937 · DOI · PMC10866706 |
| Purely Covalent Molecular Cages and Containers for Guest Encapsulation | 2022 | Review article Design not recorded in structured metadata | 140 | cc by PMID 35867555 · DOI · PMC9413269 |
| An expanded codebook of human transcription factor DNA-binding specificity | 2026 | Research article Design not recorded in structured metadata | 4 | cc by PMID 42557334 · DOI · PMC13538051 |
Fragment binding to the Nsp3 macrodomain of SARS-CoV-2 identified through crystallographic screening and computational docking [1]
Abstract reading summary — source excerpts
- Opening excerpt
- The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) macrodomain within the nonstructural protein 3 counteracts host-mediated antiviral adenosine diphosphate-ribosylation signaling.
- Closing excerpt
- The 234 fragment structures explore a wide range of chemotypes and provide starting points for development of potent SARS-CoV-2 macrodomain inhibitors.
- 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 (149 words)
The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) macrodomain within the nonstructural protein 3 counteracts host-mediated antiviral adenosine diphosphate-ribosylation signaling. This enzyme is a promising antiviral target because catalytic mutations render viruses nonpathogenic. Here, we report a massive crystallographic screening and computational docking effort, identifying new chemical matter primarily targeting the active site of the macrodomain. Crystallographic screening of 2533 diverse fragments resulted in 214 unique macrodomain-binders. An additional 60 molecules were selected from docking more than 20 million fragments, of which 20 were crystallographically confirmed. X-ray data collection to ultra-high resolution and at physiological temperature enabled assessment of the conformational heterogeneity around the active site. Several fragment hits were confirmed by solution binding using three biophysical techniques (differential scanning fluorimetry, homogeneous time-resolved fluorescence, and isothermal titration calorimetry). The 234 fragment structures explore a wide range of chemotypes and provide starting points for development of potent SARS-CoV-2 macrodomain inhibitors.
Abstract reproduced from the open-access article under the recorded cc by licence; © the authors. PMID 33853786 · DOI · PMC8046379
The energetic and allosteric landscape for KRAS inhibition [2]
Abstract reading summary — source excerpts
- Opening excerpt
- Thousands of proteins have been validated genetically as therapeutic targets for human diseases1.
- Closing excerpt
- Using the approach described here, it should be possible to rapidly and comprehensively identify allosteric target sites in many proteins.
- 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 (231 words)
Thousands of proteins have been validated genetically as therapeutic targets for human diseases1. However, very few have been successfully targeted, and many are considered 'undruggable'. This is particularly true for proteins that function via protein-protein interactions-direct inhibition of binding interfaces is difficult and requires the identification of allosteric sites. However, most proteins have no known allosteric sites, and a comprehensive allosteric map does not exist for any protein. Here we address this shortcoming by charting multiple global atlases of inhibitory allosteric communication in KRAS. We quantified the effects of more than 26,000 mutations on the folding of KRAS and its binding to six interaction partners. Genetic interactions in double mutants enabled us to perform biophysical measurements at scale, inferring more than 22,000 causal free energy changes. These energy landscapes quantify how mutations tune the binding specificity of a signalling protein and map the inhibitory allosteric sites for an important therapeutic target. Allosteric propagation is particularly effective across the central β-sheet of KRAS, and multiple surface pockets are genetically validated as allosterically active, including a distal pocket in the C-terminal lobe of the protein. Allosteric mutations typically inhibit binding to all tested effectors, but they can also change the binding specificity, revealing the regulatory, evolutionary and therapeutic potential to tune pathway activation. Using the approach described here, it should be possible to rapidly and comprehensively identify allosteric target sites in many proteins.
Abstract reproduced from the open-access article under the recorded cc by licence; © the authors. PMID 38109937 · DOI · PMC10866706
Purely Covalent Molecular Cages and Containers for Guest Encapsulation [3]
Abstract reading summary — source excerpts
- Opening excerpt
- Cage compounds offer unique binding pockets similar to enzyme-binding sites, which can be customized in terms of size, shape, and functional groups to point toward the cavity and many other parameters.
- Closing excerpt
- This review explores the progress made in the field of fully organic molecular cages and containers by focusing on the properties of the cavity and their application to encapsulate guests.
- 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 (119 words)
Cage compounds offer unique binding pockets similar to enzyme-binding sites, which can be customized in terms of size, shape, and functional groups to point toward the cavity and many other parameters. Different synthetic strategies have been developed to create a toolkit of methods that allow preparing tailor-made organic cages for a number of distinct applications, such as gas separation, molecular recognition, molecular encapsulation, hosts for catalysis, etc. These examples show the versatility and high selectivity that can be achieved using cages, which is impossible by employing other molecular systems. This review explores the progress made in the field of fully organic molecular cages and containers by focusing on the properties of the cavity and their application to encapsulate guests.
Abstract reproduced from the open-access article under the recorded cc by licence; © the authors. PMID 35867555 · DOI · PMC9413269
An expanded codebook of human transcription factor DNA-binding specificity [4]
Abstract reading summary — source excerpts
- Opening excerpt
- Gene expression is regulated by transcription factors (TFs), which recognize specific DNA sequence motifs.
- Closing excerpt
- In summary, this new codebook provides an important step forward in decoding the human genome.
- 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 (181 words)
Gene expression is regulated by transcription factors (TFs), which recognize specific DNA sequence motifs. Several hundred putative human TFs, identified mainly by an apparent DNA-binding domain, lack known binding motifs1. Furthermore, even for well-characterized TFs, it remains controversial the degree to which motifs accurately reflect binding sites in living cells2. Here we describe a systematic effort ('Codebook') to determine the sequence specificity of 332 putative and poorly characterized human TFs. More than 4,000 independent experiments, encompassing multiple in vitro and in vivo assays, produced motifs for just over half (177; 53%) of the TFs, of which most are associated with only a single protein. These results extend the vocabulary of sequence recognition encoded by human TFs by around 130 distinct motifs. Moreover, binding motifs identified in vitro are strongly enriched in cellular binding sites. Collectively, the data reveal tens of thousands of previously unknown, conserved and direct TF-binding sites across the human genome. These sites are concentrated in promoter regions and are predictive of gene expression. In summary, this new codebook provides an important step forward in decoding the human genome.
Abstract reproduced from the open-access article under the recorded cc by licence; © the authors. PMID 42557334 · DOI · PMC13538051
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 The multilayered complexity of ceRNA crosstalk and competition [5]
- Research article Allostery in disease and in drug discovery [6]
- Research article The structure of protein-protein recognition sites [7]
- Research article Allostery and cooperativity revisited [8]
- Research article The pyruvate dehydrogenase complexes: structure-based function and regulation [9]
- Research article Ligand binding assays at equilibrium: validation and interpretation [10]
References
- Schuller M, Correy GJ, Gahbauer S, Fearon D, Wu T, Díaz RE, et al.. Fragment binding to the Nsp3 macrodomain of SARS-CoV-2 identified through crystallographic screening and computational docking. . 2021. PMID 33853786 · DOI · PMC8046379
- Weng C, Faure AJ, Escobedo A, Lehner B. The energetic and allosteric landscape for KRAS inhibition. . 2024. PMID 38109937 · DOI · PMC10866706
- Montà-González G, Sancenón F, Martínez-Máñez R, Martí-Centelles V. Purely Covalent Molecular Cages and Containers for Guest Encapsulation. . 2022. PMID 35867555 · DOI · PMC9413269
- Jolma A, Laverty KU, Fathi A, Yang AWH, Yellan I, Vorontsov IE, et al.. An expanded codebook of human transcription factor DNA-binding specificity. . 2026. PMID 42557334 · DOI · PMC13538051
- Tay Y, Rinn J, Pandolfi PP. The multilayered complexity of ceRNA crosstalk and competition. Nature. 2014. PMID 24429633 · DOI · PMC4113481
- Nussinov R, Tsai CJ. Allostery in disease and in drug discovery. Cell. 2013. PMID 23582321 · DOI
- Janin J, Chothia C. The structure of protein-protein recognition sites. J Biol Chem. 1990. PMID 2204619 · DOI
- Cui Q, Karplus M. Allostery and cooperativity revisited. Protein Sci. 2008. PMID 18560010 · DOI · PMC2492820
- Patel MS, Nemeria NS, Furey W, Jordan F. The pyruvate dehydrogenase complexes: structure-based function and regulation. J Biol Chem. 2014. PMID 24798336 · DOI · PMC4059105
- Hulme EC, Trevethick MA. Ligand binding assays at equilibrium: validation and interpretation. Br J Pharmacol. 2010. PMID 20132208 · DOI · PMC3000649
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.
See how EvidenceLib is built. Spotted an error? Email support@evidencehelix.com.
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.