The DOI matches its Crossref record; 69 of the 71 references it cites were found in a registry or an index.
Anatomy of hot spots in protein interfaces
Abstract
Binding of one protein to another is involved in nearly all biological functions, yet the principles governing the interaction of proteins are not fully understood. To analyze the contributions of individual amino acid residues in protein-protein binding we have compiled a database of 2325 alanine mutants for which the change in free energy of binding upon mutation to alanine has been measured (available at http://motorhead. ucsf.edu/thorn/hotspot). Our analysis shows that at the level of side-chains there is little correlation between buried surface area and free energy of binding. We find that the free energy of binding is not evenly distributed across interfaces; instead, there are hot spots of binding energy made up of a small subset of residues in the dimer interface. These hot spots are enriched in tryptophan, tyrosine and arginine, and are surrounded by energetically less important residues that most likely serve to occlude bulk solvent from the hot spot. Occlusion of solvent is found to be a necessary condition for highly energetic interactions.
Overview
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
In the citing paper
“Protein-protein interfaces are characterized by the existence of hot spots or ‘hot regions’ in interacting regions instead of an even contribution across all contact areas.371,476,487,492–495”
From Protein Ensembles: How Does Nature Harness Thermodynamic Fluctuations for Life? The Diverse Functional Roles of Conformational Ensembles in the Cell (2016) · cites this paper as [495]
In the citing paper
“The latter two are experimental hot‐spots41 (Supporting Information Tables S2 and S8) and the third one is a candidate for experimental verification.”
From iSEE: Interface structure, evolution, and energy-based machine learning predictor of binding affinity changes upon mutations (2019) · cites this paper as [41]
Citations
Cites
MOLSCRIPT: a program to produce both detailed and schematic plots of protein structures
Kraulis, P. J. (1991) · Journal of Applied Crystallography · doi:10.1107/s0021889891004399 · Cited by 14,011
The protein data bank: A computer-based archival file for macromolecular structures
Bernstein, F. C., Koetzle, T. F., Williams, G. J. B., Meyer, E. F., Brice, M. D., Rodgers, J. R., Kennard, O., Shimanouchi, T., & Tasumi, M. (1977) · Journal of Molecular Biology · doi:10.1016/s0022-2836(77)80200-3 · Cited by 8,574
Principles of protein-protein interactions
Jones, S., & Thornton, J. M. (1996) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.93.1.13 · Cited by 2,684
Raster3D Version 2.0. A program for photorealistic molecular graphics
Merritt, E. A., & Murphy, M. E. P. (1994) · Acta Crystallographica Section D Biological Crystallography · doi:10.1107/s0907444994006396 · Cited by 2,493
Stability of Proteins Small Globular Proteins
Privalov, P. L. (1979) · Advances in protein chemistry · doi:10.1016/s0065-3233(08)60460-x · Cited by 2,163
A Hot Spot of Binding Energy in a Hormone-Receptor Interface
Clackson, T., & Wells, J. A. (1995) · Science · doi:10.1126/science.7529940 · Cited by 1,987
High-Resolution Epitope Mapping of hGH-Receptor Interactions by Alanine-Scanning Mutagenesis
Cunningham, B. C., & Wells, J. A. (1989) · Science · doi:10.1126/science.2471267 · Cited by 1,361
Shape Complementarity at Protein/Protein Interfaces
Lawrence, M. C., & Colman, P. M. (1993) · Journal of Molecular Biology · doi:10.1006/jmbi.1993.1648 · Cited by 1,224
Shape complementarity at protein–protein interfaces
Norel, R., Lin, S. L., Wolfson, H. J., & Nussinov, R. (1994) · Biopolymers · doi:10.1002/bip.360340711 · Cited by 1,208
An Evolutionary Trace Method Defines Binding Surfaces Common to Protein Families
Lichtarge, O., Bourne, H. R., & Cohen, F. E. (1996) · Journal of Molecular Biology · doi:10.1006/jmbi.1996.0167 · Cited by 1,196
Research works printed but not linked: 2
- Judice, 1997, Small molecule inhibitors of human growth hormone/receptor binding, FASEB J., 11, A839
- Schreiber, 1995, Energetics of protein-protein interactions, J. Mol. Biol., 248, 478, 10.1006/jmbi.1995.0235 · DOI
Cited by
Sorted by citations
Water as an active constituent in cell biology
Ball, P. (2008) · Chemical Reviews · doi:10.1021/cr068037a · Cited by 2,177
The atomic structure of protein-protein recognition sites 1 1Edited by A. R. Fersht
Conte, L. L., Chothia, C., & Janin, J. (1999) · Journal of Molecular Biology · doi:10.1006/jmbi.1998.2439 · Cited by 1,967
Small-molecule inhibitors of protein–protein interactions: progressing towards the dream
Arkin, M. R., & Wells, J. A. (2004) · Nature Reviews Drug Discovery · doi:10.1038/nrd1343 · Cited by 1,705
Principles of docking: An overview of search algorithms and a guide to scoring functions
Halperin, I., Ma, B., Wolfson, H., & Nussinov, R. (2002) · Proteins: Structure, Function, and Bioinformatics · doi:10.1002/prot.10115 · Cited by 1,294
Gohlke, H., Kiel, C., & Case, D. A. (2003) · Journal of Molecular Biology · doi:10.1016/s0022-2836(03)00610-7 · Cited by 1,205
Metadata
- Authors
- Bogan, A. A., & Thorn, K. S.
- Affiliations
- University of California, San Francisco (US)
- Corresponding author
- Bogan, Andrew A
- ORCID
- Thorn, Kurt S
- Venue
- Journal of Molecular Biology
- Publisher
- Elsevier BV
- Published
- 1998-07
- Volume
- 280
- Issue
- 1
- Pages
- 1-9
- ISSN
- 0022-2836 (ISSN-L)
- OpenAlex
- W2051710717
- Cited by
- 1,988
- References
- 71
- Citations by year
- 2026: 62 · 2025: 52 · 2024: 68 · 2023: 40 · 2022: 51 · 2021: 75 · 2020: 69 · 2019: 65 · 2018: 77 · 2017: 75 · 2016: 94 · 2015: 105 · 2014: 88 · 2013: 110 · 2012: 112
- FWCI
- 11.85
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Journal of Molecular Biology (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Structure and Dynamics
- Physical Sciences › Chemistry › Physical and Theoretical Chemistry › thermodynamics and calorimetric analyses
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Structural Biology › Enzyme Structure and Function
- Keywords
- protein-protein binding, binding hot spots, alanine scanning, binding free energy, protein interfaces, buried surface area, tryptophan, tyrosine, L-arginine, dimer interface, binding energy distribution
- MeSH terms
- Alanine, Amino Acids, Binding Sites, Humans, Protein Binding, Proteins, Structure-Activity Relationship
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
