ArticleJournal of the American Chemical Society2016
Dynamic and Electrostatic Effects on the Reaction Catalyzed by HIV-1 Protease.
Article in Journal of the American Chemical Society, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 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
26 citing papers in PubMed, 78 citations in OpenAlex.
- Macrocyclic geminal diols: synthesis, structures, stability and photophysical properties.Chemical science · 2026Article
- Dynamic shift of internal electric field accelerates enzymatic polyethylene terephthalate depolymerization.Communications chemistry · 2026Article
- Selective Protonation of Catalytic Dyad for γ-Secretase-Mediated Hydrolysis Revealed by Multiscale Simulations.The journal of physical chemistry. B · 2024Article
- Electrostatic Preorganization in Three Distinct Heterogeneous Proteasome β-Subunits.ACS catalysis · 2024Article
- Electric Fields Are a Key Determinant of Carbapenemase Activity in Class A β-Lactamases.ACS catalysis · 2024Article
- Electrostatics as a Guiding Principle in Understanding and Designing Enzymes.Journal of chemical theory and computation · 2024Review
- Free Energy Profile Decomposition Analysis for QM/MM Simulations of Enzymatic Reactions.Journal of chemical theory and computation · 2023Article
- Bacterial Proteases as Potentially Exploitable Modulators of SARS-CoV-2 Infection: Logic from the Literature, Informatics, and Inspiration from the Dog.Biotech (Basel (Switzerland)) · 2023Article
- Structure, Mutagenesis, and QM:MM Modeling of 3-Ketosteroid ΔBiochemistry · 2023Article
- The Binding of Different Substrate Molecules at the Docking Site and the Active Site of γ-Secretase Can Trigger Toxic Events in Sporadic and Familial Alzheimer's Disease.International journal of molecular sciences · 2023Article
- Computational design of an amidase by combining the best electrostatic features of two promiscuous hydrolases.Chemical science · 2022Article
- Structural Analysis of the Simultaneous Activation and Inhibition of γ-Secretase Activity in the Development of Drugs for Alzheimer's Disease.Pharmaceutics · 2021Article
- Mechanism of inhibition of SARS-CoV-2 MChemical science · 2020Article
- Visualizing Tetrahedral Oxyanion Bound in HIV-1 Protease Using Neutrons: Implications for the Catalytic Mechanism and Drug Design.ACS omega · 2020Article
- Protein electrostatics: From computational and structural analysis to discovery of functional fingerprints and biotechnological design.Computational and structural biotechnology journal · 2020Review
- Heavy Enzymes and the Rational Redesign of Protein Catalysts.Chembiochem : a European journal of chemical biology · 2019Article
- Loss of Hyperconjugative Effects Drives Hydride Transfer during Dihydrofolate Reductase Catalysis.ACS catalysis · 2019Article
- Modification of Enzyme Activity by Vibrational Strong Coupling of Water.Angewandte Chemie (International ed. in English) · 2019Article
- AnACS catalysis · 2019Article
- Experimental and Computational Studies Delineate the Role of Asparagine 177 in Hydride Transfer for E. coli Thymidylate Synthase.ACS catalysis · 2018Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
3 authors at 2 institutions in 2 countries.
Funding
Abstract
HIV-1 Protease (HIV-1 PR) is one of the three enzymes essential for the replication process of HIV-1 virus, which explains why it has been the main target for design of drugs against acquired immunodeficiency syndrome (AIDS). This work is focused on exploring the proteolysis reaction catalyzed by HIV-1 PR, with special attention to the dynamic and electrostatic effects governing its catalytic power. Free energy surfaces for all possible mechanisms have been computed in terms of potentials of mean force (PMFs) within hybrid QM/MM potentials, with the QM subset of atoms described at semiempirical (AM1) and DFT (M06-2X) level. The results suggest that the most favorable reaction mechanism involves formation of a gem-diol intermediate, whose decomposition into the product complex would correspond to the rate-limiting step. The agreement between the activation free energy of this step with experimental data, as well as kinetic isotope effects (KIEs), supports this prediction. The role of the protein dynamic was studied by protein isotope labeling in the framework of the Variational Transition State Theory. The predicted enzyme KIEs, also very close to the values measured experimentally, reveal a measurable but small dynamic effect. Our calculations show how the contribution of dynamic effects to the effective activation free energy appears to be below 1 kcal·mol
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.