ArticleACS catalysis2017
Exploring the Development of Ground-State Destabilization and Transition-State Stabilization in Two Directed Evolution Paths of Kemp Eliminases.
Article in ACS catalysis, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed.
- Physics-based modeling in the new era of enzyme engineering.Nature computational science · 2025Review
- Biochemical and Computational Characterization of Haloalkane Dehalogenase Variants Designed by Generative AI: Accelerating the SJournal of the American Chemical Society · 2025Article
- Unravelling Enzymatic Features in a Supramolecular Iridium Catalyst by Computational Calculations.Chemistry (Weinheim an der Bergstrasse, Germany) · 2022Article
- Natural Evolution Provides Strong Hints about Laboratory Evolution of Designer Enzymes.Proceedings of the National Academy of Sciences of the United States of America · 2022Article
- Evolution of Enzyme Function and the Development of Catalytic Efficiency: Triosephosphate Isomerase, Jeremy R. Knowles, and W. John Albery.Biochemistry · 2021Article
- Evolution of dynamical networks enhances catalysis in a designer enzyme.Nature chemistry · 2021Article
- Catalytic Principles from Natural Enzymes and Translational Design Strategies for Synthetic Catalysts.ACS central science · 2021Review
- Ground-State Destabilization by Active-Site Hydrophobicity Controls the Selectivity of a Cofactor-Free Decarboxylase.Journal of the American Chemical Society · 2020Article
- The Energetic Origin of Different Catalytic Activities in Temperature-Adapted Trypsins.ACS omega · 2020Article
- Harnessing Conformational Plasticity to Generate Designer Enzymes.Journal of the American Chemical Society · 2020Review
- Enhancing aChemical science · 2020Article
- Combinatorial Approach for Exploring Conformational Space and Activation Barriers in Computer-Aided Enzyme Design.ACS catalysis · 2020Article
- Bottom-Up Nonempirical Approach To Reducing Search Space in Enzyme Design Guided by Catalytic Fields.Journal of chemical theory and computation · 2020Article
- How the Destabilization of a Reaction Intermediate Affects Enzymatic Efficiency: The Case of Human Transketolase.ACS catalysis · 2020Article
- Exploring the challenges of computational enzyme design by rebuilding the active site of a dehalogenase.Proceedings of the National Academy of Sciences of the United States of America · 2019Article
- Exploring the Drug Resistance of HCV Protease.The journal of physical chemistry. B · 2017Article
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4 authors.
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Abstract
Computer-aided enzyme design presents a major challenge since in most cases it has not resulted in an impressive catalytic power. The reasons for the problems with computational design include the use of nonquantitative approaches, but they may also reflect other difficulties that are not completely obvious. Thus, it is very useful to try to learn from the trend in directed evolution experiments. Here we explore the nature of the refinement of Kemp eliminases by directed evolution, trying to gain an understanding of related requirements from computational design. The observed trend in the directed evolution refinement of KE07 and HG3 are reproduced, showing that in the case of KE07 the directed evolution leads to ground-state destabilization, whereas in the case of HG3 the directed evolution leads to transition-state stabilization. The nature of the different paths of the directed evolution is examined and discussed. The present study seems to indicate that computer-aided enzyme design may require more than calculations of the effect of single mutations and should be extended to calculations of the effect of simultaneous multiple mutations (that make a few residues preorganized effectively). However, the analysis of two known evolution paths can still be accomplished using the relevant sequences and structures. Thus, by comparing two directed evolution paths of Kemp eliminases we reached the important conclusion that the more effective path leads to transition-state stabilization.
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