ArticleThe Journal of chemical physics2015
Energy landscape of LeuT from molecular simulations.
Article in The Journal of chemical physics, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 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
24 citing papers in PubMed, 42 citations in OpenAlex.
- Dissecting Large-Scale Structural Transitions in Membrane Transporters Using Advanced Simulation Technologies.The journal of physical chemistry. B · 2025Review
- Exploring the Structural Dynamics of LeuT Using EPR Spectroscopy: A Focus on Transmembrane Helix 10.Journal of neurochemistry · 2025Article
- Navigating structure-based drug discovery with emerging innovations in physics- and knowledge-based approaches.npj drug discovery · 2025Review
- Tackling Hysteresis in Conformational Sampling: How to Be Forgetful with MEMENTO.Journal of chemical theory and computation · 2023Article
- The substrate import mechanism of the human serotonin transporter.Biophysical journal · 2022Article
- Sampling of Protein Conformational Space Using Hybrid Simulations: A Critical Assessment of Recent Methods.Frontiers in molecular biosciences · 2022Article
- The high-energy transition state of the glutamate transporter homologue GltPh.The EMBO journal · 2021Article
- Heteromeric Solute Carriers: Function, Structure, Pathology and Pharmacology.Advances in experimental medicine and biology · 2021Review
- Towards gaining sight of multiscale events: utilizing network models and normal modes in hybrid methods.Current opinion in structural biology · 2020Review
- The Amino Terminus of LeuT Changes Conformation in an Environment Sensitive Manner.Neurochemical research · 2020Article
- Proton Control of Transitions in an Amino Acid Transporter.Biophysical journal · 2019Article
- Molecular Basis of the Glucose Transport Mechanism in Plants.ACS central science · 2019Article
- Multiscale Simulations of Biological Membranes: The Challenge To Understand Biological Phenomena in a Living Substance.Chemical reviews · 2019Article
- Quantitative Assessment of the Energetics of Dopamine Translocation by Human Dopamine Transporter.The journal of physical chemistry. B · 2018Article
- A partially-open inward-facing intermediate conformation of LeuT is associated with NaNature communications · 2018Article
- Protein dynamic communities from elastic network models align closely to the communities defined by molecular dynamics.PloS one · 2018Article
- Allosteric modulation of human dopamine transporter activity under conditions promoting its dimerization.The Journal of biological chemistry · 2017Article
- A novel proton transfer mechanism in the SLC11 family of divalent metal ion transporters.Scientific reports · 2017Article
- Effect of Dimerization on the Dynamics of Neurotransmitter:Sodium Symporters.The journal of physical chemistry. B · 2017Article
- Conformational dynamics of a neurotransmitter:sodium symporter in a lipid bilayer.Proceedings of the National Academy of Sciences of the United States of America · 2017Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
4 authors at 2 institutions in 2 countries.
Funding
Abstract
The bacterial sodium-coupled leucine transporter (LeuT) has been broadly used as a structural model for understanding the structure-dynamics-function of mammalian neurotransmitter transporters as well as other solute carriers that share the same fold (LeuT fold), as the first member of the family crystallographically resolved in multiple states: outward-facing open, outward-facing occluded, and inward-facing open. Yet, a complete picture of the energy landscape of (sub)states visited along the LeuT transport cycle has been elusive. In an attempt to visualize the conformational spectrum of LeuT, we performed extensive simulations of LeuT dimer dynamics in the presence of substrate (Ala or Leu) and co-transported Na(+) ions, in explicit membrane and water. We used both conventional molecular dynamics (MD) simulations (with Anton supercomputing machine) and a recently introduced method, collective MD, that takes advantage of collective modes of motions predicted by the anisotropic network model. Free energy landscapes constructed based on ∼40 μs trajectories reveal multiple substates occluded to the extracellular (EC) and/or intracellular (IC) media, varying in the levels of exposure of LeuT to EC or IC vestibules. The IC-facing transmembrane (TM) helical segment TM1a shows an opening, albeit to a smaller extent and in a slightly different direction than that observed in the inward-facing open crystal structure. The study provides insights into the spectrum of conformational substates and paths accessible to LeuT and highlights the differences between Ala- and Leu-bound substates.
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.