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Record W4405675148 · doi:10.1101/2024.12.17.628075

AlphaFold prediction and analysis of Adhesion-family G protein coupled receptor (aGPCR) structures

2024· preprint· en· W4405675148 on OpenAlexaff
Xiaolong Zhou, Eddie Chen, Rithwik Ramachandran

Bibliographic record

VenuebioRxiv (Cold Spring Harbor Laboratory) · 2024
Typepreprint
Languageen
FieldBiochemistry, Genetics and Molecular Biology
TopicReceptor Mechanisms and Signaling
Canadian institutionsWestern University
Fundersnot available
KeywordsAdhesionComputational biologyChemistryBiology

Abstract

fetched live from OpenAlex

Abstract Adhesion GPCRs (aGPCRs), a family of 33 receptors, regulate crucial physiological processes through a unique self-activation mechanism. We employed AlphaFold, a state-of-the-art AI system, to predict 3D structures of aGPCRs in active and inactive conformations. Full-length models were obtained from the AlphaFold Protein Structure Database, while tethered-ligand (TL) exposed structures were predicted using AlphaFold. Comparison with available experimentally solved structures were made to validate accuracy of Alphafold aGPCR model. For receptors without experimentally solved structures, we compare structures of inactive (TL masked) and active (TL exposed) aGPCRs. In the active structures, the tethered-ligand was docked in the transmembrane bundle for several receptors but surprisingly not all receptors. This AI driven analysis of aGPCR structures provides a framework for exploring alternative receptor activation mechanisms. These models also offer valuable insights into receptor conformational changes and TL interactions, paving the way for the development of novel pharmacological tools and accelerating drug discovery efforts targeting this important receptor family.

Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.

How this classification was reachedexpand

Full frame machine prediction

Teacher imitation

Not calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.

metaresearch head score (Codex)0.001
metaresearch head score (Gemma)0.001
Version: metacan-v3-hybrid-931329e0061cValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Simulation or modeling · Consensus signal: Simulation or modeling
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.002
Threshold uncertainty score0.008

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0010.001
Meta-epidemiology (narrow)0.0010.000
Meta-epidemiology (broad)0.0010.001
Bibliometrics0.0010.001
Science and technology studies0.0000.000
Scholarly communication0.0010.001
Open science0.0010.000
Research integrity0.0010.001
Insufficient payload (model declined to judge)0.0020.001

Machine scores (provisional)

The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.

Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.

Opus teacher head0.009
GPT teacher head0.214
Teacher spread0.205 · how far apart the two teachers sit on this one work
Validation statusscore_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it

Classification

machine, unvalidated

Machine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.

The models applied no category: nothing in the taxonomy fit this work.
Study designSimulation or modeling
Domainnot available
GenreEmpirical

How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".

Quick stats

Citations1
Published2024
Admission routes1
Has abstractyes

Explore more

Same venuebioRxiv (Cold Spring Harbor Laboratory)→Same topicReceptor Mechanisms and Signaling→French-language works237,207→