ArticleJournal of molecular graphics & modelling2012
Insights from molecular dynamics: the binding site of cocaine in the dopamine transporter and permeation pathways of substrates in the leucine and dopamine transporters.
Article in Journal of molecular graphics & modelling, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 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
13 citing papers in PubMed, 21 citations in OpenAlex.
- Revealing the location and dynamics of a concealed binding site in the dopamine transporter.Nature communications · 2025Article
- Analysis of the Methylation Level of theInternational journal of molecular sciences · 2023Article
- Molecular mechanisms of action of stimulant novel psychoactive substances that target the high-affinity transporter for dopamine.Neuronal signaling · 2021Review
- Feasible Classified Models for Parkinson Disease fromSensors (Basel, Switzerland) · 2019Article
- Modulation of Hippocampal Antioxidant Defense System in Chronically Stressed Rats by Lithium.Oxidative medicine and cellular longevity · 2019Article
- Inhibitor mechanisms in the S1 binding site of the dopamine transporter defined by multi-site molecular tethering of photoactive cocaine analogs.Biochemical pharmacology · 2017Article
- The Environment Shapes the Inner Vestibule of LeuT.PLoS computational biology · 2016Article
- Properties of an inward-facing state of LeuT: conformational stability and substrate release.Biophysical journal · 2015Article
- Monoamine transporters: insights from molecular dynamics simulations.Frontiers in pharmacology · 2015Review
- Insights to ligand binding to the monoamine transporters-from homology modeling to LeuBAT and dDAT.Frontiers in pharmacology · 2015Review
- Computational and biochemical docking of the irreversible cocaine analog RTI 82 directly demonstrates ligand positioning in the dopamine transporter central substrate-binding site.The Journal of biological chemistry · 2014Article
- Structural dynamics of the monoamine transporter homolog LeuT from accelerated conformational sampling and channel analysis.Proteins · 2014Article
- Changes in dopamine transporter binding in nucleus accumbens following chronic self-administration cocaine: heroin combinations.Synapse (New York, N.Y.) · 2014Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
2 authors at 1 institution in 1 country.
Funding
Abstract
The dopamine transporter (DAT) facilitates the regulation of synaptic neurotransmitter levels. As a target for therapeutic and illicit psycho-stimulant drugs like antidepressants and cocaine, DAT has been studied intensively. Despite a wealth of mutational and physiological data regarding DAT, the structure remains unsolved and details of the transport mechanism, binding sites and conformational changes remain debated. A bacterial homolog of DAT, the leucine transporter (LeuT(Aa)) has been used as a template and framework for modeling and understanding DAT. Free energy profiles obtained from Multi-Configuration Thermodynamic Integration simulations allowed us to correctly identify the primary and secondary binding pockets of LeuT(Aa). A comparison of free energy profiles for dopamine and cocaine in DAT suggests that the binding site of cocaine is located in a secondary pocket, not the primary substrate site. Two recurring primary pathways for intracellular substrate release from the primary pocket are identified in both transporters using the Random Acceleration Molecular Dynamics method. One pathway appears to follow transmembranes (TMs) 1a and 6b while the other pathway follows along TMs 6b and 8. Interestingly, we observe that a single sodium ion is co-transported with leucine during both simulation types.
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.