ArticleProceedings of the National Academy of Sciences of the United States of America2019
Exploring the challenges of computational enzyme design by rebuilding the active site of a dehalogenase.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
16 citing papers in PubMed.
- Decoding Enzymatic Dechlorination with Multiscale Modeling: Mechanistic Insights into Native Haloalkane Dehalogenase fromACS catalysis · 2025Article
- Investigation of Electrostatic Effects on Enyzme Catalysis: Insights from Computational Simulations of Monoamine Oxidase A Pathological Variants Leading to the Brunner Syndrome.Journal of chemical information and modeling · 2025Article
- Biochemical and Computational Characterization of Haloalkane Dehalogenase Variants Designed by Generative AI: Accelerating the SJournal of the American Chemical Society · 2025Article
- Mechanisms and Opportunities for Rational In Silico Design of Enzymes to Degrade Per- and Polyfluoroalkyl Substances (PFAS).Journal of chemical information and modeling · 2023Review
- Enhancing luciferase activity and stability through generative modeling of natural enzyme sequences.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- Brunner syndrome caused by point mutation explained by multiscale simulation of enzyme reaction.Scientific reports · 2022Article
- Computational design of an amidase by combining the best electrostatic features of two promiscuous hydrolases.Chemical science · 2022Article
- The catalytic mechanism of the mitochondrial methylenetetrahydrofolate dehydrogenase/cyclohydrolase (MTHFD2).PLoS computational biology · 2022Article
- Essential Functional Interplay of the Catalytic Groups in Acid Phosphatase.ACS catalysis · 2022Article
- Redesigning Enzymes for Biocatalysis: Exploiting Structural Understanding for Improved Selectivity.Frontiers in molecular biosciences · 2022Review
- Probing the Suitability of Different CaMolecules (Basel, Switzerland) · 2021Article
- Biomolecular Modeling and Simulation: A Prospering Multidisciplinary Field.Annual review of biophysics · 2021Article
- Substrate specificity of 2-deoxy-D-ribose 5-phosphate aldolase (DERA) assessed by different protein engineering and machine learning methods.Applied microbiology and biotechnology · 2020Article
- Enhancing aChemical science · 2020Article
- Combinatorial Approach for Exploring Conformational Space and Activation Barriers in Computer-Aided Enzyme Design.ACS catalysis · 2020Article
- Fluorescent substrates for haloalkane dehalogenases: Novel probes for mechanistic studies and protein labeling.Computational and structural biotechnology journal · 2020Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
6 authors.
Funding
Abstract
Rational enzyme design presents a major challenge that has not been overcome by computational approaches. One of the key challenges is the difficulty in assessing the magnitude of the maximum possible catalytic activity. In an attempt to overcome this challenge, we introduce a strategy that takes an active enzyme (assuming that its activity is close to the maximum possible activity), design mutations that reduce the catalytic activity, and then try to restore that catalysis by mutating other residues. Here we take as a test case the enzyme haloalkane dehalogenase (DhlA), with a 1,2-dichloroethane substrate. We start by demonstrating our ability to reproduce the results of single mutations. Next, we design mutations that reduce the enzyme activity and finally design double mutations that are aimed at restoring the activity. Using the computational predictions as a guide, we conduct an experimental study that confirms our prediction in one case and leads to inconclusive results in another case with 1,2-dichloroethane as substrate. Interestingly, one of our predicted double mutants catalyzes dehalogenation of 1,2-dibromoethane more efficiently than the wild-type enzyme.
Indexed as
Identifiers
What OpenQuestion holds
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.