ArticleChemical science2017
Quantified electrostatic preorganization in enzymes using the geometry of the electron charge density.
Article in Chemical science, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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Who cites it
24 citing papers in PubMed, 68 citations in OpenAlex.
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- Electric Field-Empowered Nanozymes: From Passive Adaptation to Active Precision Therapy.Advanced materials (Deerfield Beach, Fla.) · 2026Review
- SOD2 is a regulator of proteasomal degradation promoting an adaptive cellular starvation response.Cell reports · 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
- Computational Insights into SARS-CoV-2 Main Protease Mutations and Nirmatrelvir Efficacy: The Effects of P132H and P132H-A173V.Journal of chemical information and modeling · 2024Article
- Distal Mutations in the β-Clamp of DNA Polymerase III* Disrupt DNA Orientation and Affect Exonuclease Activity.Journal of the American Chemical Society · 2023Article
- Brunner syndrome caused by point mutation explained by multiscale simulation of enzyme reaction.Scientific reports · 2022Article
- Convergence in determining enzyme functional descriptors across Kemp eliminase variants.Electronic structure (Bristol, England) · 2022Article
- Oriented internal electrostatic fields: an emerging design element in coordination chemistry and catalysis.Chemical science · 2022Review
- ElectrostaticChemical science · 2022Article
- Why Monoamine Oxidase B Preferably MetabolizesInternational journal of molecular sciences · 2022Article
- Advances in optimizing enzyme electrostatic preorganization.Current opinion in structural biology · 2022Review
- Direct Aerobic Generation of a Ferric Hydroperoxo Intermediate Via a Preorganized Secondary Coordination Sphere.Journal of the American Chemical Society · 2021Article
- Catalytic Fields as a Tool to Analyze Enzyme Reaction Mechanism Variants and Reaction Steps.The journal of physical chemistry. B · 2021Article
- Cheminformatic quantum mechanical enzyme model design: A catechol-O-methyltransferase case study.Biophysical journal · 2021Article
- Electric Fields in Catalysis: From Enzymes to Molecular Catalysts.ACS catalysis · 2021Article
- Toxic and Physiological Metal Uptake and Release by Human Serum Transferrin.Biophysical journal · 2020Article
- Electrostatic Environment of Proteorhodopsin Affects the pKa of Its Buried Primary Proton Acceptor.Biophysical journal · 2020Article
- Installation of internal electric fields by non-redox active cations in transition metal complexes.Chemical science · 2019Article
Corrections and comments
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Authors and funding
4 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Electrostatic preorganization is thought to be a principle factor responsible for the impressive catalytic capabilities of enzymes. The full protein structure is believed to facilitate catalysis by exerting a highly specific electrostatic field on the active site. Computationally determining the extent of electrostatic preorganization is a challenging process. We propose using the topology and geometry of the electron charge density in the enzyme's active site to asses the effects of electrostatic preorganization. In support of this approach we study the convergence of features of the charge density as the size of the active site model increases in Histone Deacetylase 8. The magnitude of charge density at critical points and most Bader atomic charges are found to converge quickly as more of the protein is included in the simulation. The exact position of critical points however, is found to converge more slowly and be strongly influenced by the protein residues that are further away from the active site. We conjecture that the positions of critical points are affected through perturbations to the wavefunctions in the active site caused by dipole moments from amino acid residues throughout the protein. We further hypothesize that electrostatic preorganization, from the point of view of charge density, can not be easily understood through the charges on atoms or the nature of the bonding interactions, but through the relative positions of critical points that are known to correlate with reactivity and reaction barriers.
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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.