ArticlePLoS computational biology2022
Engineering indel and substitution variants of diverse and ancient enzymes using Graphical Representation of Ancestral Sequence Predictions (GRASP).
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 40 papers.
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40 citing papers in PubMed, 61 citations in OpenAlex.
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- Investigation of Substrate Specificity in 5-Keto-4-Deoxy-Glucarate Dehydratase and 2-Keto-3-Deoxy-L-Arabinonate Dehydratase.Chembiochem : a European journal of chemical biology · 2026Article
- Ancestral Protein Reconstruction Uncovers a Thermotolerant Rieske Oxygenase with EnhancedACS synthetic biology · 2026Article
- Structural insights into pterocarpan reductases unveil a universal ring-opening mechanism in plant biosynthesis of 4-(furan-2-yl) phenol derivatives.Acta pharmaceutica Sinica. B · 2026Article
- Thermostable ancestors enabled evolutionary diversification of promiscuous chemical defence enzymes.The EMBO journal · 2026Article
- Ancestral functionality and symbiotic refinement of NIN in root nodule symbiosis.Nature communications · 2026Article
- Conformations and sequence determinants in the lipid binding of an adhesive peptide derived from Vibrio cholerae biofilms.PLoS pathogens · 2026Article
- Widespread promiscuous alkaline phosphatases underscore ancient microbial phosphite utilization.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Logan: Planetary-Scale Genome Assembly Surveys Life's Diversity.bioRxiv : the preprint server for biology · 2025Article
- Positive selection at core genes may underlie niche adaptation in Fusobacterium animalis.Gut pathogens · 2025Article
- Algorithms to reconstruct past indels: The deletion-only parsimony problem.PLoS computational biology · 2025Article
- Accelerated Pseudogenization in the Ancient Endosymbionts of Giant Scale Insects.Molecular biology and evolution · 2025Article
- Computational scoring and experimental evaluation of enzymes generated by neural networks.Nature biotechnology · 2025Article
- ASR gene family: a case of tandem-drive evolution.Frontiers in molecular biosciences · 2025Article
- Gene expression and evolution of Bowman-Birk protease inhibitors in wild and domesticatedFrontiers in plant science · 2025Article
- Convergent evolution of the G3BP1-binding motif in betacoronavirus nucleocapsid proteins.Virus evolution · 2025Article
- Ancestral Sequence Reconstruction for Designing Biocatalysts and Investigating their Functional Mechanisms.JACS Au · 2024Review
- Evolutionary insights into the stereoselectivity of imine reductases based on ancestral sequence reconstruction.Nature communications · 2024Article
- Do protein language models learn phylogeny?Briefings in bioinformatics · 2024Article
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Authors and funding
22 authors at 3 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Ancestral sequence reconstruction is a technique that is gaining widespread use in molecular evolution studies and protein engineering. Accurate reconstruction requires the ability to handle appropriately large numbers of sequences, as well as insertion and deletion (indel) events, but available approaches exhibit limitations. To address these limitations, we developed Graphical Representation of Ancestral Sequence Predictions (GRASP), which efficiently implements maximum likelihood methods to enable the inference of ancestors of families with more than 10,000 members. GRASP implements partial order graphs (POGs) to represent and infer insertion and deletion events across ancestors, enabling the identification of building blocks for protein engineering. To validate the capacity to engineer novel proteins from realistic data, we predicted ancestor sequences across three distinct enzyme families: glucose-methanol-choline (GMC) oxidoreductases, cytochromes P450, and dihydroxy/sugar acid dehydratases (DHAD). All tested ancestors demonstrated enzymatic activity. Our study demonstrates the ability of GRASP (1) to support large data sets over 10,000 sequences and (2) to employ insertions and deletions to identify building blocks for engineering biologically active ancestors, by exploring variation over evolutionary time.
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