ArticleACS chemical neuroscience2014
Atomic and dynamic insights into the beneficial effect of the 1,4-naphthoquinon-2-yl-L-tryptophan inhibitor on Alzheimer's Aβ1-42 dimer in terms of aggregation and toxicity.
Article in ACS chemical neuroscience, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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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.
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Who cites it
18 citing papers in PubMed, 75 citations in OpenAlex.
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- Targeting MERTK tyrosine kinase: Virtual screening and molecular dynamics insights for anti-cancer drug development.PloS one · 2025Article
- Alzheimer's Disease Protein Targets: Comprehensive Review and Future Directions.Current pharmaceutical design · 2025Review
- Dynamics of Amyloid Formation from Simplified Representation to Atomistic Simulations.Methods in molecular biology (Clifton, N.J.) · 2022Article
- Computer Simulations Aimed at Exploring Protein Aggregation and Dissociation.Methods in molecular biology (Clifton, N.J.) · 2022Article
- Journey on Naphthoquinone and Anthraquinone Derivatives: New Insights in Alzheimer's Disease.Pharmaceuticals (Basel, Switzerland) · 2021Review
- Protein storytelling through physics.Science (New York, N.Y.) · 2020Review
- Naphthoquinone Tryptophan Hybrids: A Promising Small Molecule Scaffold for Mitigating Aggregation of Amyloidogenic Proteins and Peptides.Frontiers in cell and developmental biology · 2019Review
- Initial Structural Models of the Aβ42 Dimer from Replica Exchange Molecular Dynamics Simulations.ACS omega · 2017Article
- Conformational Ensembles of the Wild-Type and S8C Aβ1-42 Dimers.The journal of physical chemistry. B · 2017Article
- Self-assembly of the full-length amyloid Aβ42 protein in dimers.Nanoscale · 2016Article
- Discovery of DNA dyes Hoechst 34580 and 33342 as good candidates for inhibiting amyloid beta formation: in silico and in vitro study.Journal of computer-aided molecular design · 2016Article
- Coupling of Zinc-Binding and Secondary Structure in Nonfibrillar Aβ40 Peptide Oligomerization.Journal of chemical information and modeling · 2015Article
- Amyloid β Protein and Alzheimer's Disease: When Computer Simulations Complement Experimental Studies.Chemical reviews · 2015Review
- Structural Conversion of Aβ17-42 Peptides from Disordered Oligomers to U-Shape Protofilaments via Multiple Kinetic Pathways.PLoS computational biology · 2015Article
- Virtual and In Vitro Screens Reveal a Potential Pharmacophore that Avoids the Fibrillization of Aβ1-42.PloS one · 2015Article
- Alzheimer's disease--a panorama glimpse.International journal of molecular sciences · 2014Review
- The OPEP protein model: from single molecules, amyloid formation, crowding and hydrodynamics to DNA/RNA systems.Chemical Society reviews · 2014Review
Corrections and comments
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Authors and funding
4 authors at 4 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Aggregation of the amyloid β protein (Aβ) peptide with 40 or 42 residues is one key feature in Alzheimer's disease (AD). The 1,4-naphthoquinon-2-yl-L-tryptophan (NQTrp) molecule was reported to alter Aβ self-assembly and reduce toxicity. Though nuclear magnetic resonance experiments and various simulations provided atomic information about the interaction of NQTrp with Aβ peptides spanning the regions of residues 12-28 and 17-42, none of these studies were conducted on the full-length Aβ1-42 peptide. To this end, we performed extensive atomistic replica exchange molecular dynamics simulations of Aβ1-42 dimer with two NQTrp molecules in explicit solvent, by using a force field known to fold diverse proteins correctly. The interactions between NQTrp and Aβ1-42, which change the Aβ interface by reducing most of the intermolecular contacts, are found to be very dynamic and multiple, leading to many transient binding sites. The most favorable binding residues are Arg5, Asp7, Tyr10, His13, Lys16, Lys18, Phe19/Phe20, and Leu34/Met35, providing therefore a completely different picture from in vitro and in silico experiments with NQTrp with shorter Aβ fragments. Importantly, the 10 hot residues that we identified explain the beneficial effect of NQTrp in reducing both the level of Aβ1-42 aggregation and toxicity. Our results also indicate that there is room to design more efficient drugs targeting Aβ1-42 dimer against AD.
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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.