Hot spots—A review of the protein–protein interface determinant amino‐acid residues
Abstract
Proteins tendency to bind to one another in a highly specific manner forming stable complexes is fundamental to all biological processes. A better understanding of complex formation has many practical applications, which include the rational design of new therapeutic agents, and the analysis of metabolic and signal transduction networks. Alanine‐scanning mutagenesis made possible the detection of the functional epitopes, and demonstrated that most of the protein–protein binding energy is related only to a group of few amino acids at intermolecular protein interfaces: the hot spots. The scope of this review is to summarize all the available information regarding hot spots for a better atomic understanding of their structure and function. The ultimate objective is to improve the rational design of complexes of high affinity and specificity as well as that of small molecules, which can mimic the functional epitopes of the proteic complexes. Proteins 2007. © 2007 Wiley‐Liss, Inc.
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Some interfacial residues (hot-spots) contribute most to binding affinity.
“Instead, some residues (hot‐spots) contribute most to the binding affinity.16, 17, 18”
From iSEE: Interface structure, evolution, and energy-based machine learning predictor of binding affinity changes upon mutations (2019) · cites this paper as [16]
Binding energy is not evenly distributed among interfacial residues.
“It has been verified that the binding energy is not evenly distributed among the interfacial residues.”
From iSEE: Interface structure, evolution, and energy-based machine learning predictor of binding affinity changes upon mutations (2019) · cites this paper as [16]
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- Authors
- Moreira, I. S., Fernandes, P. A., & Ramos, M. J.
- Affiliations
- Universidade do Porto (PT)
- Corresponding author
- Ramos, Maria J.
- Venue
- Proteins: Structure, Function, and Bioinformatics
- Publisher
- Wiley
- Published
- 2007-06
- Volume
- 68
- Issue
- 4
- Pages
- 803-812
- ISSN
- 0887-3585 (ISSN-L)
- 1097-0134
- OpenAlex
- W2136206140
- Cited by
- 760
- References
- 118
- Citations by year
- 2026: 28 · 2025: 30 · 2024: 30 · 2023: 38 · 2022: 39 · 2021: 40 · 2020: 41 · 2019: 44 · 2018: 43 · 2017: 36 · 2016: 36 · 2015: 46 · 2014: 49 · 2013: 68 · 2012: 59
- FWCI
- 2.16
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Proteins Structure Function and Bioinformatics (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Structure and Dynamics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Interaction Studies and Fluorescence Analysis
- Physical Sciences › Materials Science › Materials Chemistry › Enzyme Structure and Function
- Keywords
- protein-protein interfaces, amino acid residues, alanine scanning, binding energy, protein complex formation, rational drug design, functional epitopes
- MeSH terms
- Amino Acids, Binding Sites, Humans, Models, Molecular, Protein Conformation, Proteins, Receptors, Somatotropin, Human Growth Hormone
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 ›
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