ArticleBiophysical journal2006
Probing a model of a GPCR/ligand complex in an explicit membrane environment: the human cholecystokinin-1 receptor.
Article in Biophysical journal, 2006. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 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
21 citing papers in PubMed.
- Genetic variants of accessory proteins and G proteins in human genetic disease.Critical reviews in clinical laboratory sciences · 2025Review
- Exploring TAS2R46 biomechanics through molecular dynamics and network analysis.Frontiers in molecular biosciences · 2024Article
- Alchemical Free Energy Calculations on Membrane-Associated Proteins.Journal of chemical theory and computation · 2023Review
- Quantum Mechanical and Molecular Mechanics Modeling of Membrane-Embedded Rhodopsins.The Journal of membrane biology · 2019Review
- Recent Trends and Applications of Molecular Modeling in GPCR⁻Ligand Recognition and Structure-Based Drug Design.International journal of molecular sciences · 2018Review
- Article
- Conformational changes in dopamine transporter intracellular regions upon cocaine binding and dopamine translocation.Neurochemistry international · 2014Article
- Computational prediction of alanine scanning and ligand binding energetics in G-protein coupled receptors.PLoS computational biology · 2014Article
- Direct demonstration of unique mode of natural peptide binding to the type 2 cholecystokinin receptor using photoaffinity labeling.Peptides · 2013Article
- Beyond modeling: all-atom olfactory receptor model simulations.Frontiers in genetics · 2012Article
- By interacting with the C-terminal Phe of apelin, Phe255 and Trp259 in helix VI of the apelin receptor are critical for internalization.The Journal of biological chemistry · 2010Article
- Ligand and structure-based methodologies for the prediction of the activity of G protein-coupled receptor ligands.Journal of computer-aided molecular design · 2009Article
- Community-wide assessment of GPCR structure modelling and ligand docking: GPCR Dock 2008.Nature reviews. Drug discovery · 2009Review
- Building a foundation for structure-based cellulosome design for cellulosic ethanol: Insight into cohesin-dockerin complexation from computer simulation.Protein science : a publication of the Protein Society · 2009Article
- Atomistic insights into regulatory mechanisms of the HER2 tyrosine kinase domain: a molecular dynamics study.Biophysical journal · 2009Article
- A juxtamembrane mutation in the N terminus of the dopamine transporter induces preference for an inward-facing conformation.Molecular pharmacology · 2009Article
- Use of multidimensional fluorescence resonance energy transfer to establish the orientation of cholecystokinin docked at the type A cholecystokinin receptor.Biochemistry · 2008Article
- Benzodiazepine ligands can act as allosteric modulators of the Type 1 cholecystokinin receptor.Bioorganic & medicinal chemistry letters · 2008Article
- Structural basis of cholecystokinin receptor binding and regulation.Pharmacology & therapeutics · 2008Review
- Exploring the binding pocket for pyridopyrimidine ligands at the CCK1 receptor by molecular docking.Journal of molecular modeling · 2008Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
6 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
A three-dimensional model structure of a complex formed by a G-protein-coupled receptor (GPCR) and an agonist ligand is probed and refined using molecular-dynamics simulations and free energy calculations in a realistic environment. The model of the human receptor of cholecystokinin associated to agonist ligand CCK9 was obtained from a synergistic procedure combining site-directed mutagenesis experiments and in silico modeling. The 31-ns molecular-dynamics simulation in an explicit membrane environment indicates that both the structure of the receptor and its interactions with the ligand are robust. Whereas the secondary structure of the alpha-helix bundle is well preserved, the region of the intracellular loops exhibits a significant flexibility likely to be ascribed to the absence of G-protein subunits in the model. New insight into the structural features of the binding pocket is gained, in particular, the interplay of the ligand with both the receptor and internal water molecules. Water-mediated interactions are shown to participate in the binding, hence, suggesting additional site-directed mutagenesis experiments. Accurate free energy calculations on mutated ligands provide differences in the receptor-ligand binding affinity, thus offering a direct, quantitative comparison to experiment. We propose that this detailed consistency-checking procedure be used as a routine refinement step of in vacuo GPCR models, before further investigation and application to structure-based drug design.
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.