ArticleNature communications2018
The evolution of multiple active site configurations in a designed enzyme.
Article in Nature communications, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 43 papers.
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Who cites it
43 citing papers in PubMed.
- Predicting Activation Barriers With Ring and Bond Critical Points in the Kemp Elimination Reaction.Chemphyschem : a European journal of chemical physics and physical chemistry · 2026Article
- MAPLE: a machine-learning force-field-native platform for automated reaction modeling and enzyme design.Chemical science · 2026Article
- Computational Method for the Detection of Communication Pathways in Enzymes that Correlate with Experimentally Defined Thermal Activation Networks.The journal of physical chemistry letters · 2026Article
- Conformational Dynamics and Catalytic Backups in a Hyper-thermostable Engineered Archaeal Protein Tyrosine Phosphatase.JACS Au · 2026Article
- Distal mutations enhance catalysis in designed enzymes by facilitating substrate binding and product release.Nature communications · 2025Article
- Opening and closing of a cryptic pocket in VP35 toggles it between two different RNA-binding modes.eLife · 2025Article
- Article
- Enzyme Enhancement Through Computational Stability Design Targeting NMR-Determined Catalytic Hotspots.Journal of the American Chemical Society · 2025Article
- Perspectives on Computational Enzyme Modeling: From Mechanisms to Design and Drug Development.ACS omega · 2024Review
- Substrate Positioning Dynamics Involves a Non-Electrostatic Component to Mediate Catalysis.The journal of physical chemistry letters · 2023Article
- Mutexa: A Computational Ecosystem for Intelligent Protein Engineering.Journal of chemical theory and computation · 2023Review
- Computational remodeling of an enzyme conformational landscape for altered substrate selectivity.Nature communications · 2023Article
- Fishing for Catalysis: Experimental Approaches to Narrowing Search Space in Directed Evolution of Enzymes.JACS Au · 2023Review
- EnzyHTP Computational Directed Evolution with Adaptive Resource Allocation.Journal of chemical information and modeling · 2023Article
- Glycosylation increases active site rigidity leading to improved enzyme stability and turnover.The FEBS journal · 2023Article
- Second-Shell Residues Contribute to Catalysis by Predominately Preorganizing the Apo State in PafA.Journal of the American Chemical Society · 2023Article
- Conformational Selection of a Tryptophan Side Chain Drives the Generalized Increase in Activity of PET Hydrolases through a Ser/Ile Double Mutation.ACS organic & inorganic Au · 2023Article
- Article
- Enzymatic Conjugation of Modified RNA Fragments by Ancestral RNA Ligase AncT4_2.Applied and environmental microbiology · 2022Article
- Convergence in determining enzyme functional descriptors across Kemp eliminase variants.Electronic structure (Bristol, England) · 2022Article
Corrections and comments
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Authors and funding
16 authors.
Funding
Abstract
Developments in computational chemistry, bioinformatics, and laboratory evolution have facilitated the de novo design and catalytic optimization of enzymes. Besides creating useful catalysts, the generation and iterative improvement of designed enzymes can provide valuable insight into the interplay between the many phenomena that have been suggested to contribute to catalysis. In this work, we follow changes in conformational sampling, electrostatic preorganization, and quantum tunneling along the evolutionary trajectory of a designed Kemp eliminase. We observe that in the Kemp Eliminase KE07, instability of the designed active site leads to the emergence of two additional active site configurations. Evolutionary conformational selection then gradually stabilizes the most efficient configuration, leading to an improved enzyme. This work exemplifies the link between conformational plasticity and evolvability and demonstrates that residues remote from the active sites of enzymes play crucial roles in controlling and shaping the active site for efficient catalysis.
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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.