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In Silico Evaluation of Haloalkylated TSPO PET Tracer Candidates for Traumatic Brain Injury Neuroinflammation

This repository contains code, processed data, figures, and supplementary materials for a computational study prioritizing haloalkylated emapunil-derived TSPO PET tracer candidates for traumatic brain injury neuroinflammation.

The workflow includes reference TSPO tracer scoring, AC-5216/emapunil pharmacophore selection, analog enumeration, CNS-MPO filtering, AutoDock Vina docking, PBPK-derived candidate ranking, and Logan graphical analysis of simulated time–activity curves.

This project is entirely computational. The proposed analogs should be interpreted as prioritized candidates for future radiosynthesis, TSPO binding assays, autoradiography, and preclinical TBI PET validation, not as experimentally validated radiotracers.

Repository Structure

  • TSPO/: AlphaFold/UniProt-derived human TSPO structural model and receptor preparation files.
  • tracers/: PubChem-derived reference tracer conformations and prepared docking inputs.
  • src/: Source code for enumeration, screening, docking analysis, PBPK aggregation, and PET kinetic analysis.
  • data_analysis/: Reference-tracer scoring and z-score analysis scripts.
  • fine_all_rounds/: Fine docking outputs for final lead candidates using a 14 × 14 × 14 grid and exhaustiveness 32.
  • error_round3/: Error correction logs and recomputed files for problematic Round 3 candidates.
  • processed_data_supplements/: Final supplementary CSV tables supporting the manuscript.
  • figures/: Manuscript and analysis figures.
  • templates_functional_groups/: Functional-group templates used for analog enumeration.
  • manuscripts/: Manuscript and supplementary information files.

Citation

Dhruv Subramanian. In Silico Evaluation of Haloalkylated Human 18kDa Translocator Protein PET Tracer Candidates for Traumatic Brain Injury Neuroinflammation. ChemRxiv. 21 May 2026. DOI: https://doi.org/10.26434/chemrxiv.15003660/v1

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In Silico Evaluation of Haloalkylated Human 18kDa Translocator Protein PET Tracer Candidates for Traumatic Brain Injury Neuroinflammation

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