ArticlePLoS computational biology2022
Are transient protein-protein interactions more dispensable?
Article in PLoS computational biology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.
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Who cites it
7 citing papers in PubMed, 17 citations in OpenAlex.
- Beyond PAD Inhibition: Emerging Avenues and Natural Products for Targeting Citrullination in Immune Diseases.Biomedicines · 2026Review
- The Constructive Neutral Evolution of Behaviour.Ecology and evolution · 2025Article
- A quantitative comparison of the deleteriousness of missense and nonsense mutations using the structurally resolved human protein interactome.Protein science : a publication of the Protein Society · 2025Article
- Ion channel traffic jams: the significance of trafficking deficiency in long QT syndrome.Cell discovery · 2025Review
- Article
- Microscale Thermophoresis as a Tool to Study Protein Interactions and Their Implication in Human Diseases.International journal of molecular sciences · 2022Review
- A microRNA-microRNA crosstalk network inferred from genome-wide single nucleotide polymorphism variants in natural populations ofFrontiers in plant science · 2022Article
Corrections and comments
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Protein-protein interactions (PPIs) are key drivers of cell function and evolution. While it is widely assumed that most permanent PPIs are important for cellular function, it remains unclear whether transient PPIs are equally important. Here, we estimate and compare dispensable content among transient PPIs and permanent PPIs in human. Starting with a human reference interactome mapped by experiments, we construct a human structural interactome by building three-dimensional structural models for PPIs, and then distinguish transient PPIs from permanent PPIs using several structural and biophysical properties. We map common mutations from healthy individuals and disease-causing mutations onto the structural interactome, and perform structure-based calculations of the probabilities for common mutations (assumed to be neutral) and disease mutations (assumed to be mildly deleterious) to disrupt transient PPIs and permanent PPIs. Using Bayes' theorem we estimate that a similarly small fraction (<~20%) of both transient and permanent PPIs are completely dispensable, i.e., effectively neutral upon disruption. Hence, transient and permanent interactions are subject to similarly strong selective constraints in the human interactome.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.