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Record W77539298 · doi:10.1007/0-306-47015-2_15

Molecular Modeling of the Interaction of Neurotrophins with the P75NTR Common Neurotrophin Receptor

2005· book-chapter· en· W77539298 on OpenAlexaff
Igor L. Shamovsky, Gregory M. Ross, Richard J. Riopelle, Donald F. Weaver

Bibliographic record

VenueKluwer Academic Publishers eBooks · 2005
Typebook-chapter
Languageen
FieldNeuroscience
TopicNerve injury and regeneration
Canadian institutionsQueen's University
FundersMedical Research Council
KeywordsNeurotrophinLow-affinity nerve growth factor receptorNerve growth factorReceptorTrk receptorNeurotrophin-3Cell biologyBinding siteNeurotrophic factorsBrain-derived neurotrophic factorTropomyosin receptor kinase CChemistryBiologyNeuroscienceBiochemistryGrowth factor

Abstract

fetched live from OpenAlex

Neurotrophins are a family of proteins with pleiotropic effects mediated by two distinct receptor types, namely the trk family and the common neurotrophin receptor p75 NTR Binding of four mammalian neurotrophins, nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), neurotrophin-3 (NT-3) and neurotrophin-4/5 (NT-4/5), to p75 NTR is studied by large scale molecular dynamics simulations using CHARMM force field. Geometric match of neurotrophin/receptor binding domains in the complexes is evaluated by the Lawrence & Colman’s shape complementarity statistic S c. The model of neurotrophin/receptor interactions suggests that the receptor binding domains of neurotrophins (loops I and IV) are geometrically and electrostatically complementary to a putative binding site of p75 NTR formed by the second and part of the third cysteine-rich domains. All charged residues within the loops I and IV of the neurotrophins, previously determined as being critical for p75 NTR binding, directly participate in receptor binding in the framework of the model. Principal residues of the binding site of p75 NTR include Asp 47, Lys 56, Asp 75, Asp 76, Asp 88 and Glu 89. The additional involvement of Arg 80 and Glu 73 is specific for NGF and BDNF, respectively, and Glu 73 participates in binding with NT-3 and NT-4/5. The model developed has utility in computer-aided molecular design.

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)0.000
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 score0.017
Threshold uncertainty score0.033

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0000.001
Meta-epidemiology (narrow)0.0010.000
Meta-epidemiology (broad)0.0010.001
Bibliometrics0.0000.001
Science and technology studies0.0010.000
Scholarly communication0.0010.000
Open science0.0010.000
Research integrity0.0020.001
Insufficient payload (model declined to judge)0.0040.001

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 head0.034
GPT teacher head0.255
Teacher spread0.221 · 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
Published2005
Admission routes1
Has abstractyes

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