ArticleCell systems2019
Epistasis in a Fitness Landscape Defined by Antibody-Antigen Binding Free Energy.
Article in Cell systems, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.
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Who cites it
30 citing papers in PubMed.
- Synthetic Approaches as Empirical Tools for Testing Evolutionary Theory.Genome biology and evolution · 2026Review
- Attribution assignment for deep-generative sequence models enables interpretability analysis using positive-only data.PLoS computational biology · 2026Article
- Machine-learning prediction of affinity and epistasis in the bovine pancreatic trypsin inhibitor-chymotrypsin complex.Protein science : a publication of the Protein Society · 2026Article
- The Convergence of Antimicrobial Resistance and Virulence inMicroorganisms · 2026Review
- Biophysical trade-offs in antibody evolution are resolved by conformation-mediated epistasis.bioRxiv : the preprint server for biology · 2026Article
- Evolutionary pathways in epistatic mechanical networks.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Article
- Graph attention with structural features improves the generalizability of identifying functional sequences at a protein interface.bioRxiv : the preprint server for biology · 2025Article
- Epistatic hotspots organize antibody fitness landscape and boost evolvability.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Antibodies and cryptographic hash functions: quantifying the specificity paradox.Frontiers in immunology · 2025Article
- Reconciling specificity and non-specificity in antibody binding: an energy landscape framework for immunology education.Frontiers in immunology · 2025Article
- The simplicity of protein sequence-function relationships.Nature communications · 2024Article
- Article
- The simplicity of protein sequence-function relationships.bioRxiv : the preprint server for biology · 2024Article
- Protein sequence landscapes are not so simple: on reference-free versus reference-based inference.bioRxiv : the preprint server for biology · 2024Article
- An in silico investigation on the binding site preference of PD-1 and PD-L1 for designing antibodies for targeted cancer therapy.PloS one · 2024Article
- Article
- Article
- Compensatory epistasis maintains ACE2 affinity in SARS-CoV-2 Omicron BA.1.Nature communications · 2022Article
- General Theory of Specific Binding: Insights from a Genetic-Mechano-Chemical Protein Model.Molecular biology and evolution · 2022Article
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Authors and funding
4 authors.
Funding
Abstract
Epistasis is the phenomenon by which the effect of a mutation depends on its genetic background. While it is usually defined in terms of organismal fitness, for single proteins, it must reflect physical interactions among residues. Here, we systematically extract the specific contribution pairwise epistasis makes to the physical affinity of antibody-antigen binding relevant to affinity maturation, a process of accelerated Darwinian evolution. We find that, among competing definitions of affinity, the binding free energy is the most appropriate to describe epistasis. We show that epistasis is pervasive, accounting for 25%-35% of variability, of which a large fraction is beneficial. This work suggests that epistasis both constrains, through negative epistasis, and enlarges, through positive epistasis, the set of possible evolutionary paths that can produce high-affinity sequences during repeated rounds of mutation and selection.
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