ArticleBiophysical journal2014
Electrostatic channeling in P. falciparum DHFR-TS: Brownian dynamics and Smoluchowski modeling.
Article in Biophysical journal, 2014. 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, 25 citations in OpenAlex.
- Crystallographic fragment-binding studies of the Mycobacterium tuberculosis trifunctional enzyme suggest binding pockets for the tails of the acyl-CoA substrates at its active sites and a potential substrate-channeling path between them.Acta crystallographica. Section D, Structural biology · 2024Article
- Drug Discovery Efforts to Identify Novel Treatments for Neglected Tropical Diseases - Cysteine Protease Inhibitors.Current medicinal chemistry · 2024Review
- Crowding within synaptic junctions influences the degradation of nucleotides by CD39 and CD73 ectonucleotidases.Biophysical journal · 2022Article
- Mechanisms and Effects of Substrate Channelling in Enzymatic Cascades.Methods in molecular biology (Clifton, N.J.) · 2022Review
- Temperature-Dependent Kinetic Isotope Effects in R67 Dihydrofolate Reductase from Path-Integral Simulations.The journal of physical chemistry. B · 2021Article
- Co-localization and confinement of ecto-nucleotidases modulate extracellular adenosine nucleotide distributions.PLoS computational biology · 2020Article
- Molecular basis for metabolite channeling in a ring opening enzyme of the phenylacetate degradation pathway.Nature communications · 2019Article
- Can enzyme proximity accelerate cascade reactions?Scientific reports · 2019Article
- Article
- Understanding ligand-receptor non-covalent binding kinetics using molecular modeling.Frontiers in bioscience (Landmark edition) · 2017Review
- Electrostatic Steering Accelerates C3d:CR2 Association.The journal of physical chemistry. B · 2016Article
- Quantifying the Influence of the Crowded Cytoplasm on Small Molecule Diffusion.The journal of physical chemistry. B · 2016Article
- Substrate channeling between the human dihydrofolate reductase and thymidylate synthase.Protein science : a publication of the Protein Society · 2016Article
- Conservation and Role of Electrostatics in Thymidylate Synthase.Scientific reports · 2015Article
- Electrostatic steering enhances the rate of cAMP binding to phosphodiesterase: Brownian dynamics modeling.Protein science : a publication of the Protein Society · 2015Article
- Enzyme localization, crowding, and buffers collectively modulate diffusion-influenced signal transduction: Insights from continuum diffusion modeling.The Journal of chemical physics · 2015Article
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
Abstract
We perform Brownian dynamics simulations and Smoluchowski continuum modeling of the bifunctional Plasmodium falciparum dihydrofolate reductase-thymidylate synthase (P. falciparum DHFR-TS) with the objective of understanding the electrostatic channeling of dihydrofolate generated at the TS active site to the DHFR active site. The results of Brownian dynamics simulations and Smoluchowski continuum modeling suggest that compared to Leishmania major DHFR-TS, P. falciparum DHFR-TS has a lower but significant electrostatic-mediated channeling efficiency (?15-25%) at physiological pH (7.0) and ionic strength (150 mM). We also find that removing the electric charges from key basic residues located between the DHFR and TS active sites significantly reduces the channeling efficiency of P. falciparum DHFR-TS. Although several protozoan DHFR-TS enzymes are known to have similar tertiary and quaternary structure, subtle differences in structure, active-site geometry, and charge distribution appear to influence both electrostatic-mediated and proximity-based substrate channeling.
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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.