Combinatorial assembly and design of enzymes
Open accessPreprint — published as 10.1126/science.ade9434 · Paper page
Abstract
Design of structurally diverse enzymes is constrained by long-range interactions that are needed for accurate folding. We introduce an atomistic and machine-learning strategy for Combinatorial Assembly and Design of ENZymes, CADENZ, to design fragments that combine with one another to generate diverse, low-energy structures with stable catalytic constellations. We applied CADENZ to endoxylanases and used activity-based protein profiling to recover thousands of active and structurally diverse enzymes. Functional designs exhibit high active-site preorganization and more stable and compact packing outside the active site. Implementing these lessons into CADENZ led to a tenfold improved hit rate and >10,000 active enzymes. This design-test-learn loop can be applied, in principle, to any modular protein family, yielding huge diversity and general lessons on protein design principles.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
Highly accurate protein structure prediction with AlphaFold
Jumper, J., Evans, R., Pritzel, A., Green, T., Figurnov, M., Ronneberger, O., Tunyasuvunakool, K., Bates, R., Žídek, A., Potapenko, A., et al. (2021) · Nature · doi:10.1038/s41586-021-03819-2 · Cited by 43,764 · see citing works
An evolution-based model for designing chorismate mutase enzymes
Russ, W. P., Figliuzzi, M., Stocker, C., Barrat-Charlaix, P., Socolich, M., Kast, P., Hilvert, D., Monasson, R., Cocco, S., Weigt, M., et al. (2020) · Science · doi:10.1126/science.aba3304 · Cited by 313 · see citing works
Flagged first, then by citations
- Authors
- Lipsh-Sokolik, R., Khersonsky, O., Schröder, S. P., de Boer, C., Hoch, S.-Y., Davies, G. J., Overkleeft, H. S., & Fleishman, S. J.
- Affiliations
- Weizmann Institute of Science (IL)
- Leiden University (NL)
- University of York (GB)
- Corresponding author
- Fleishman, Sarel J.
- ORCID
- Venue
- bioRxiv (Cold Spring Harbor Laboratory)
- Publisher
- openRxiv
- Published
- 2022-09-18
- OpenAlex
- W4296352113
- Cited by
- 2
- References
- 2
- Citations by year
- 2023: 1 · 2022: 1
- Type
- posted content
- Language
- en
- Open access
- green
- doi.org
- Licence
- cc-by-nc-nd
- Locations
- bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion, cc-by-nc-nd)
- White Rose Research Online (University of Leeds, The University of Sheffield, University of York) (submittedVersion)
- Funders
- Volkswagen Foundation (94747)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Structure and Dynamics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Enzyme Catalysis and Immobilization
- Physical Sciences › Materials Science › Materials Chemistry › Enzyme Structure and Function
- Keywords
- enzyme design, endoxylanase, protein folding, long-range interactions, activity-based protein profiling, protein stability
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
