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A Semi-Quantitative Drug Affinity Responsive Target Stability (DARTS) assay for studying Rapamycin/mTOR interaction
Published on: August 27, 2019
DORSSAA: Drug-Target interactOmics Resource Based on Stability/Solubility Alteration Assay.
Ehsan Zangene1, Elham Gholizadeh1, Veit Schwämmle2
1Department of Pharmacology, University of Helsinki, Helsinki, Finland.
We developed DORSSAA, a web platform integrating drug-protein interaction data from stability and solubility assays. This resource aids in discovering drug targets and understanding drug mechanisms more reliably.
Area of Science:
- Proteomics
- Pharmacology
- Bioinformatics
Background:
- High-throughput methods like Thermal Proteome Profiling (TPP) and Proteome Integral Solubility Alteration (PISA) advance drug-protein interaction studies.
- A unified platform for analyzing stability and solubility alteration data is lacking, hindering cross-study comparisons.
Purpose of the Study:
- Introduce DORSSAA (Drug-target interactOmics Resource based on Stability/Solubility Alteration Assay), a web platform for analyzing drug-protein interactions.
- Facilitate systematic analysis and visualization of proteome stability and solubility alteration assay datasets.
Main Methods:
- Developed an interactive and expandable web-based platform, DORSSAA.
- Integrated 1,135,985 records from 38 cell lines/organisms, 135 compounds, and 40,742 protein targets.
- Utilized case studies for methotrexate target profiling and combinatorial therapy in leukemia.
Main Results:
- DORSSAA enables comparative drug-protein interaction analysis and therapeutic target discovery.
- Demonstrated utility in identifying protein-drug interactions across diverse experimental contexts.
- Provides direct, statistically controlled, protein-level evidence of drug mechanisms.
Conclusions:
- DORSSAA accelerates drug discovery by enabling reliable identification of drug targets and off-target effects.
- Enhances understanding of protein behavior and facilitates the discovery of potential drug combinations.
- Offers a superior approach compared to existing databases by providing direct mechanistic evidence.
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