ArticleProceedings of the National Academy of Sciences of the United States of America2016
Hierarchy and extremes in selections from pools of randomized proteins.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed.
- How far can you go? Extrapolating values of catalytic activity from known protein landscapes in natural and directed evolution.Chemical Society reviews · 2026Review
- Diversity Scale of Library Matters: Impact of mRNA Library Diversity Scales on the Discovery of Macrocyclic Peptides Targeting a Protein by the RaPID System.ACS central science · 2025Article
- Inference and design of antibody specificity: From experiments to models and back.PLoS computational biology · 2024Article
- Unsupervised modeling of mutational landscapes of adeno-associated viruses viability.BMC bioinformatics · 2024Article
- Inference of annealed protein fitness landscapes with AnnealDCA.PLoS computational biology · 2024Article
- ACIDES: on-line monitoring of forward genetic screens for protein engineering.Nature communications · 2023Article
- Germline-encoded specificities and the predictability of the B cell response.PLoS pathogens · 2023Article
- The Origin of Life: What Is the Question?Astrobiology · 2022Article
- AMaLa: Analysis of Directed Evolution Experiments via Annealed Mutational Approximated Landscape.International journal of molecular sciences · 2021Article
- Parameters and determinants of responses to selection in antibody libraries.PLoS computational biology · 2021Article
- Unsupervised Inference of Protein Fitness Landscape from Deep Mutational Scan.Molecular biology and evolution · 2021Article
- Thresholds in Origin of Life Scenarios.iScience · 2020Review
- Review
- Evolving generalists in switching rugged landscapes.PLoS computational biology · 2019Article
- Epistasis in a Fitness Landscape Defined by Antibody-Antigen Binding Free Energy.Cell systems · 2019Article
- Phage display peptide libraries: deviations from randomness and correctives.Nucleic acids research · 2018Article
- Clonal Heterogeneity Influences the Fate of New Adaptive Mutations.Cell reports · 2017Article
- Article
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Authors and funding
6 authors.
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Abstract
Variation and selection are the core principles of Darwinian evolution, but quantitatively relating the diversity of a population to its capacity to respond to selection is challenging. Here, we examine this problem at a molecular level in the context of populations of partially randomized proteins selected for binding to well-defined targets. We built several minimal protein libraries, screened them in vitro by phage display, and analyzed their response to selection by high-throughput sequencing. A statistical analysis of the results reveals two main findings. First, libraries with the same sequence diversity but built around different "frameworks" typically have vastly different responses; second, the distribution of responses of the best binders in a library follows a simple scaling law. We show how an elementary probabilistic model based on extreme value theory rationalizes the latter finding. Our results have implications for designing synthetic protein libraries, estimating the density of functional biomolecules in sequence space, characterizing diversity in natural populations, and experimentally investigating evolvability (i.e., the potential for future evolution).
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