ArticleNature biotechnology2012
Increased Diels-Alderase activity through backbone remodeling guided by Foldit players.
Article in Nature biotechnology, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 78 papers, 1 of them a synthesis that pooled it.
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Who cites it
78 citing papers in PubMed, 1 synthesis or guideline pooled it.
- Crowdsourcing--harnessing the masses to advance health and medicine, a systematic review.Journal of general internal medicine · 2014Pooled it
- Crowdsourcing malaria parasite quantification: an online game for analyzing images of infected thick blood smears.Journal of medical Internet research · 2012Trial
- Building Molecules by a Self-Replicator That Catalyzes Acyl Hydrazone Formation.Angewandte Chemie (International ed. in English) · 2026Article
- Drugit: crowd-sourcing molecular design of non-peptidic VHL binders.Nature communications · 2025Article
- An evolved artificial radical cyclase enables the construction of bicyclic terpenoid scaffolds via an H-atom transfer pathway.Nature chemistry · 2024Article
- A Perspective on Crowdsourcing and Human-in-the-Loop Workflows in Precision Health.Journal of medical Internet research · 2024Article
- The evolutionary origin of naturally occurring intermolecular Diels-Alderases from Morus alba.Nature communications · 2024Article
- Strategies for designing biocatalysts with new functions.Chemical Society reviews · 2024Review
- Evolutionary Engineering of a Cp*Rh(III) Complex-Linked Artificial Metalloenzyme with a Chimeric β-Barrel Protein Scaffold.Journal of the American Chemical Society · 2023Article
- The road to fully programmable protein catalysis.Nature · 2022Review
- Crowdsourced RNA design discovers diverse, reversible, efficient, self-contained molecular switches.Proceedings of the National Academy of Sciences of the United States of America · 2022Article
- A Brave New World: Virtual Reality and Augmented Reality in Systems Biology.Frontiers in bioinformatics · 2022Article
- Mechanism of the Stereoselective Catalysis of Diels-Alderase PyrE3 Involved in Pyrroindomycin Biosynthesis.Journal of the American Chemical Society · 2022Article
- Engineering an efficient and enantioselective enzyme for the Morita-Baylis-Hillman reaction.Nature chemistry · 2022Article
- Building enzymes from scratch.Nature chemistry · 2022Article
- Exo-selective intermolecular Diels-Alder reaction by PyrI4 and AbnU on non-natural substrates.Communications chemistry · 2021Article
- The Potential Role of School Citizen Science Programs in Infectious Disease Surveillance: A Critical Review.International journal of environmental research and public health · 2021Review
- Synthetic Formatotrophs for One-Carbon Biorefinery.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2021Review
- Assessing the difficulty of annotating medical data in crowdworking with help of experiments.PloS one · 2021Article
- Hybrid methods for combined experimental and computational determination of protein structure.The Journal of chemical physics · 2020Review
18 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
10 authors.
Funding
Abstract
Computational enzyme design holds promise for the production of renewable fuels, drugs and chemicals. De novo enzyme design has generated catalysts for several reactions, but with lower catalytic efficiencies than naturally occurring enzymes. Here we report the use of game-driven crowdsourcing to enhance the activity of a computationally designed enzyme through the functional remodeling of its structure. Players of the online game Foldit were challenged to remodel the backbone of a computationally designed bimolecular Diels-Alderase to enable additional interactions with substrates. Several iterations of design and characterization generated a 24-residue helix-turn-helix motif, including a 13-residue insertion, that increased enzyme activity >18-fold. X-ray crystallography showed that the large insertion adopts a helix-turn-helix structure positioned as in the Foldit model. These results demonstrate that human creativity can extend beyond the macroscopic challenges encountered in everyday life to molecular-scale design problems.
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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.