Understand CB1R
Recognize the receptor as a membrane signaling system whose response depends on ligand, receptor state, cellular context, and experimental design.
PAGE MISSION
Understand the question before reading the result
This page is designed for people who want to understand how CB1R–THC modulation can be investigated with high-performance computational tools, structural bioinformatics, and molecular simulation. It connects receptor biology, ligand recognition, membrane context, temporal behavior, and scientific uncertainty in one guided path.
Read the model
Follow how an experimental structure and a THC pose become a computational system that can be inspected over time.
Interpret responsibly
Distinguish visualization, simulation-derived observables, experimental evidence, and biological inference before drawing conclusions.
SYSTEM CONTEXT
From structural data to a molecular trajectory
5XRA is the structural source for the receptor preparation. Its crystallographic ligand is AM11542; THC was introduced separately as the ligand of the local docking and dynamics workflow. The resulting trajectory is a computational model for structural investigation and hypothesis generation.
Receptor
5XRA-derived CB1R preparation, cleaned and used as a rigid docking receptor.
RCSB structural record ↗Ligand
THC, PubChem CID 16078, prepared locally with a GAFF2-compatible parameter set.
- Formula
- C₂₁H₃₀O₂
- Molar mass
- 314.46 g·mol⁻¹
- Local model
- 53 atoms · 55 bonds
Environment
POPC/CHL1 bilayer, TIP3P water, ff19SB protein, Lipid21 membrane, and GAFF2 ligand parameters.
Question
How do receptor shape, ligand contacts, and the membrane environment change across a simulated trajectory?
STUDY MATURITY
A record that becomes stronger by stages
The presentation's version map is retained here as an editorial control: each milestone describes what the project can responsibly expose at that point.
- 0.1Preparation and dockingDocumented
Docking, ligand parameters, membrane construction, diagnostics, minimization, and heating.
- 0.2Restricted equilibration and reviewCurrent record
Outputs through the 300–400 ps analysis window, quality controls, and molecular visualizations.
- 0.3Production dynamicsPlanned
Longer sampling, independent replicas, and consolidated trajectory processing.
- 1.0Technical reportPlanned
Reproducible scripts, complete provenance, and conclusions bounded by the evidence.
What does molecular dynamics actually simulate?
A molecular-dynamics trajectory numerically propagates atomic positions and velocities under a selected force field. It can reveal relaxation, fluctuations, contacts, and environmental response within the model.
It does not automatically establish experimental affinity, physiological efficacy, or convergence. Those claims require validated preparation, adequate sampling, controls, and independent replicas.
How were the visual selections made in PyMOL?
SELECT RECEPTOR, CB1R_THC AND POLYMER.PROTEIN
SELECT THC, CB1R_THC AND RESN THC
SELECT MEMBRANE, CB1R_THC AND RESN PA+PC+OL+CHLThe visual convention uses cyan/teal for CB1R, cyan carbon atoms and red oxygen atoms for THC, and yellow for the membrane. The animation is a visualization of the model and is not itself a stability test.
MOLECULAR VISUALIZATION
See the system at the scale of the model
Visual records supplied from the CB1R–THC membrane analysis. Use the gallery to move from the full environment to the receptor and ligand, then open the animations to inspect the recorded motion.
READING THE IMAGE
From environment to interaction
The membrane surrounds the receptor as a yellow molecular network; CB1R is rendered in cyan and THC is visible in the orthosteric pocket. The image communicates composition and viewpoint, not trajectory convergence.
MembraneCB1RTHC
RECORDED MOTION
Explore the supplied animations
These videos are visualizations of the computational system. They should not be interpreted as an independent validation of binding or stability.
COMPUTATIONAL WORKFLOW
Follow the evidence chain
Select a stage to see what was performed, what is available, and what the result cannot establish.
STRUCTURAL PROVENANCE
Establish the receptor context before the pose
The local computational directory identifies 5XRA as the receptor source. Its construct, mutations, fragment coverage, and original ligand context remain part of the interpretation.
Evidence statusSource identified; construct, mutations, and fragment coverage remain part of the interpretation.
POSE GENERATION
Rigid-receptor docking of THC
AutoDock Vina 1.2.5 generated nine modes with exhaustiveness 8 in a 24 Å cubic search box. The best reported score is −11.21 kcal·mol⁻¹.
Evidence statusExecuted calculation; the score ranks poses and is not an experimental affinity.
MEMBRANE PREPARATION
Embed the pose in a mixed lipid environment
The selected THC pose was combined with POPC/CHL1, TIP3P water, and neutralizing chloride ions. The documented build used 14 Cl⁻ and did not add a target salt concentration.
Evidence statusSystem construction is documented; protonation and final topology require explicit review.
PRELIMINARY RELAXATION
Minimize, heat, and equilibrate
Minimization, heating to 310 K, NPT stages, and a semi-isotropic membrane stage are present in the local output. Files corresponding to the 300–400 ps window are also available.
Evidence statusPreliminary execution available; not yet a validated production trajectory.
OBSERVABLES
Measure behavior without overstating certainty
RMSD, RMSF, THC heavy-atom RMSD, contacts, and box dimensions were extracted for the 300–400 ps analysis window. “Native contacts” refer to the initial pose definition.
Evidence statusDescriptive analysis available; convergence and reproducibility remain open questions.
NPT · REAL CHECKPOINTS
How the box and system respond over time
The NPT stage allows the simulation cell to respond while temperature and pressure are controlled. Move through the checkpoints extracted from the local analysis to compare volume, temperature, membrane thickness, and THC–CB1R contacts.
302 ps400 ps
Values are reported checkpoints from the files summary.TEMP, summary.VOLUME, box_dimensions.dat, and contacts_count.dat. The box and contact records are indexed by analysis frame.
Temperature310.11 Ktarget: 310 K
Volume948,550.14 ųreported system volume
Box Z94.30 Åanalysis frame 1
Contacts131 / 0native / non-native
RESULTS REGISTER
What the current files support
The values below are a compact editorial index of the local record. They are not a substitute for the original topology, coordinates, trajectories, or logs.
kcal·mol⁻¹ · Vina pose 1
ps · preliminary trajectory record
K · equilibration target
0 M added salt concentration
System build97,244 atoms
declashed system record; a separate final build contains 98,718 atoms.
Backbone RMSD≈ 0.20–0.22 Å
reported in the inspected 300–400 ps window.
THC heavy-atom RMSD≈ 0.27 Å
after CB1R fit in the same window.
Contact definitionInitial pose
the “native” reference is computational, not experimental.
TECHNICAL REVIEW
A completed command is not yet a validated model
The study is usable as a traceable preliminary record, provided its unresolved preparation choices remain visible.
What is available
- 5XRA-derived receptor and THC docking outputs.
- Mixed-lipid membrane system with TIP3P water.
- Minimization, heating, NPT, and semi-isotropic stages.
- RMSD, RMSF, contact, ligand, and box analyses.
What remains open
- Confirm CYS154–CYS161 in the final topology; it is declared in the preparation record.
- Review protonation because automatic protonation was skipped.
- Separate neutralization ions from a physiological salt protocol.
- Resolve receptor-file mismatch between docking configuration and log.
- Establish production sampling, replicas, and convergence.
WHY THIS WORKFLOW MATTERS
Potential value across different contexts
Structural bioinformatics, molecular visualization, simulation, experimental evidence, and biological inference are distinct levels of information. Keeping them separate makes future analytical layers more useful.
Structure–activity questions
Computational models can organize hypotheses about recognition, selectivity, conformational change, and ligand–receptor contacts before experimental testing.
Data-supported discovery
Curated structural records can support ligand comparison, rational compound design, analysis workflows, and reproducible research and development practices.
Evidence-aware communication
Clear boundaries between models and biological conclusions can strengthen scientific education, risk communication, harm-reduction discussions, and evidence-based policy dialogue.
EVIDENCE BOUNDARY
What this case study does not claim
Docking proposes a pose hypothesis; it does not prove binding affinity or residence time.
A 300–400 ps analysis window does not establish long-timescale convergence or a unique binding mode.
5XRA is the local structural source, but its AM11542-bound experimental context is not evidence that THC was crystallized there.
Read the CB1R molecular-dynamics context · Read the docking interpretation