Amino acid-base interactions: A three-dimensional analysis of protein-DNA interactions at an atomic level
Open accessAbstract
To assess whether there are universal rules that govern amino acid-base recognition, we investigate hydrogen bonds, van der Waals contacts and water-mediated bonds in 129 protein-DNA complex structures. DNA-backbone interactions are the most numerous, providing stability rather than specificity. For base interactions, there are significant base-amino acid type correlations, which can be rationalised by considering the stereochemistry of protein side chains and the base edges exposed in the DNA structure. Nearly two-thirds of the direct read-out of DNA sequences involves complex networks of hydrogen bonds, which enhance specificity. Two-thirds of all protein-DNA interactions comprise van der Waals contacts, compared to about one-sixth each of hydrogen and water-mediated bonds. This highlights the central importance of these contacts for complex formation, which have previously been relegated to a secondary role. Although common, water-mediated bonds are usually non-specific, acting as space-fillers at the protein-DNA interface. In conclusion, the majority of amino acid-base interactions observed follow general principles that apply across all protein-DNA complexes, although there are individual exceptions. Therefore, we distinguish between interactions whose specificities are 'universal' and 'context-dependent'. An interactive Web-based atlas of side chain-base contacts provides access to the collected data, including analyses and visualisation of the three-dimensional geometry of the interactions.
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Glycine interacts far more favorably with purine than with pyrimidine based on observed protein-DNA interactions.
“Based on the observed contact between amino acids in a protein and bases in DNA, glycine interacts far more favorably with purine than with pyrimidine [92].”
From Detailed Dissection and Critical Evaluation of the Pfizer/BioNTech and Moderna mRNA Vaccines (2021) · cites this paper as [92]
The Hydrogen bonds section reports that glycine makes some interactions, and the van der Waals contacts section says its overall contact frequency is as expected. Neither section compares glycine’s interactions with purines and pyrimidines; searches for glycine with the individual bases and for a purine preference found no such comparison in our copy. (LLM, conf=0.73)
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Research works printed but not linked: 3
- Seeman,N.C., Rosenberg,J.M. and Rich,A. (1976) Sequence-specific recognition of double helical nucleic acids by proteins. Proc. Natl Acad. Sci. USA, 73, 804-808.
- Jones,S. and Thornton,J.M. (1996) Principles of protein-protein interactions. Proc. Natl Acad. Sci. USA, 93, 13-20.
- Singh,J. and Thornton,J.M. (1992) Atlas of Protein Side-Chain Interactions. IRL Press, Oxford, Vols I and II.
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- Authors
- Luscombe, N. M.
- Affiliations
- University College London (GB)
- Corresponding author
- Luscombe, N. M.
- ORCID
- Luscombe, N. M.
- Venue
- Nucleic Acids Research
- Publisher
- Oxford University Press (OUP)
- Published
- 2001-07-01
- Volume
- 29
- Issue
- 13
- Pages
- 2860-2874
- ISSN
- 0305-1048 (ISSN-L)
- 1362-4962
- PMC
- PMC55782
- OpenAlex
- W2137154596
- Cited by
- 981
- References
- 0
- Citations by year
- 2026: 26 · 2025: 50 · 2024: 41 · 2023: 40 · 2022: 33 · 2021: 47 · 2020: 33 · 2019: 42 · 2018: 39 · 2017: 44 · 2016: 51 · 2015: 47 · 2014: 43 · 2013: 43 · 2012: 45
- FWCI
- 8.05
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Nucleic Acids Research (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- UCL Discovery (University College London) (submittedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › DNA and Nucleic Acid Chemistry
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Structure and Dynamics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA and protein synthesis mechanisms
- Keywords
- protein-DNA interactions, hydrogen bonding, van der Waals contacts, base specificity, protein-DNA complex structure
- MeSH terms
- DNA, DNA-Binding Proteins, Hydrogen Bonding, Nucleic Acid Conformation, Protein Binding, Protein Conformation, Software, Substrate Specificity, Water, Sequence Homology, Amino Acid, Databases as Topic, Base Pairing, Internet, Static Electricity
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