ArticlePLoS computational biology2019
Key residues in TLR4-MD2 tetramer formation identified by free energy simulations.
Article in PLoS computational biology, 2019. 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.
- Evaluation of toll-like receptor inhibition by novel thymoquinone analogues as potential remedy for diabetic nephropathy.Molecular diversity · 2026Article
- Immunoinformatic-based design of a multi-epitope subunit vaccine against Ruminococcus torques using subtractive proteomics and molecular dynamics simulations.Scientific reports · 2026Article
- In silico framework for designing and validating a multi-stage subunit vaccine against Tuberculosis using reverse vaccinology approach.PloS one · 2026Article
- Integrative in vitro and in silico evaluation of HSP60-derived peptides as immunomodulators of the TLR4/MD-2 complex.Scientific reports · 2025Article
- Systems biology and microbiome innovations for personalized diabetic retinopathy management.NPJ systems biology and applications · 2025Review
- Computational Identification and Anti-Inflammatory Evaluation of T19093 as a TLR4/MD2 Inhibitor.Current topics in medicinal chemistry · 2025Article
- Insights into the gut-liver axis: mechanisms and emerging therapies in hepatocellular carcinoma.Frontiers in pharmacology · 2025Review
- Amine headgroups in ionizable lipids drive immune responses to lipid nanoparticles by binding to the receptors TLR4 and CD1d.Nature biomedical engineering · 2024Article
- Unveiling the multifaceted role of toll-like receptors in immunity of aquatic animals: pioneering strategies for disease management.Frontiers in immunology · 2024Review
- A drug repurposing endeavor to discover a multi-targeting ligand against RhlR and LasR proteins from opportunistic human pathogen Pseudomonas aeruginosa.Journal of molecular modeling · 2022Article
- Review
- Fighting Against Bacterial Lipopolysaccharide-Caused Infections through Molecular Dynamics Simulations: A Review.Journal of chemical information and modeling · 2021Review
- Aureusidin derivative CNQX inhibits chronic colitis inflammation and mucosal barrier damage by targeting myeloid differentiation 2 protein.Journal of cellular and molecular medicine · 2021Article
- Structural Changes beyond the EF-Hand Contribute to Apparent Calcium Binding Affinities: Insights from Parvalbumins.The journal of physical chemistry. B · 2021Article
- Recent Developments in Free Energy Calculations for Drug Discovery.Frontiers in molecular biosciences · 2021Review
- TLR4-Targeting Therapeutics: Structural Basis and Computer-Aided Drug Discovery Approaches.Molecules (Basel, Switzerland) · 2020Review
Corrections and comments
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Authors and funding
2 authors.
Funding
Abstract
Toll-like receptors (TLRs) play a central role in both the innate and adaptive immune systems by recognizing pathogen-associated molecular patterns and inducing the release of the effector molecules of the immune system. The dysregulation of the TLR system may cause various autoimmune diseases and septic shock. A series of molecular dynamics simulations and free energy calculations were performed to investigate the ligand-free, lipopolysaccharide (LPS)-bound, and neoseptin3-bound (TLR4-MD2)2 tetramers. Compared to earlier simulations done by others, our simulations showed that TLR4 structure was well maintained with stable interfaces. Free energy decomposition by molecular mechanics Poisson-Boltzmann surface area (MM-PBSA) method suggests critical roles that two hydrophobic clusters I85-L87-P88 and I124-L125-P127 of MD2, together with LPS and neoseptin3, may play in TLR4 activation. We propose that 1) direct contacts between TLR4 convex surface and LPS and neoseptin3 at the region around L442 significantly increase the binding and 2) binding of LPS and neoseptin3 in the central hydrophobic cavity of MD2 triggers burial of F126 and exposure of I85-L87-P88 that facilitate formation of (TLR4-MD2)2 tetramer and activation of TLR4 system.
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What Socratic 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 Socratic graph.