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Combined Quantitative and Qualitative Statistical Analyses Improve Benzodiazepine Target Discovery in Label-free
Lydia H Griggs1, Doo Nam Kim1, Damon T Leach1
1Biological Sciences Division, Pacific Northwest National Laboratory, Richland, Washington 99352, United States.
Journal of Proteome Research
|March 14, 2026
Summary
We developed chemoprotR, an R package for analyzing affinity-based protein profiling (AfBPP) data, and used it to identify benzodiazepine drug targets in the brain, revealing novel protein interactions.
Area of Science:
- Proteomics
- Neuroscience
- Pharmacology
Background:
- Affinity-based protein profiling (AfBPP) identifies protein targets of small molecules.
- Label-free AfBPP can yield data with high missingness, complicating analysis.
- Benzodiazepine interactions extend beyond GABAA receptors, but targets are not fully understood.
Purpose of the Study:
- To develop an R package, chemoprotR, for quantitative and qualitative analysis of AfBPP data.
- To identify specific brain protein targets of benzodiazepines using AfBPP.
- To evaluate the utility of benzodiazepine affinity-based probes (AfBPs) and statistical analysis for target identification.
Main Methods:
- Developed the R package chemoprotR for chemoproteomic data analysis.
- Synthesized benzodiazepine AfBPs and applied them to rat brain synaptosomes.
- Utilized competitive labeling with flurazepam and analyzed presence-absence data.
Main Results:
- Identified GABAA receptor subunits and other ion channel proteins as benzodiazepine targets.
- FR-DA, a flurazepam-based probe, yielded more significant targets than flunitrazepam-based probes.
- Demonstrated effective target identification using AfBPs and competitive binding assays.
Conclusions:
- chemoprotR facilitates robust analysis of AfBPP data, including challenging datasets with missing values.
- Benzodiazepine AfBPs successfully identified known and potential novel protein targets in the brain.
- Combined statistical approaches are crucial for interpreting AfBPP data and discovering drug-protein interactions.
