Discovering the landscape of protein modifications
E Keith Keenan1, Derek K Zachman2, Matthew D Hirschey3
1Duke Molecular Physiology Institute and Sarah W. Stedman Nutrition and Metabolism Center, Duke University Medical Center, Durham, NC 27701, USA; Department of Pharmacology & Cancer Biology, Duke University Medical Center, Durham, NC 27710, USA.
This review explores the history and current state of protein modifications, highlighting how new computational tools will accelerate the discovery and functional analysis of these crucial cellular processes.
Area of Science:
- Biochemistry
- Molecular Biology
- Proteomics
Background:
- Protein modifications are essential for cellular functions across all domains of life.
- Early research in the 20th century identified non-canonical amino acids through chemical hydrolysis.
- Mass-spectrometry-based proteomics has led to the discovery of over 500 distinct protein modifications.
Purpose of the Study:
- To review the historical discovery of key post-translational modifications.
- To quantify the current landscape of covalent protein adducts.
- To assess the future role of computational tools in discovering new protein modifications and their functions.
Main Methods:
- Historical literature review of protein modification discoveries.
- Quantitative analysis of the known landscape of covalent protein adducts.
- Assessment of emerging computational tools (data science, machine learning, AI) in proteomics.
Main Results:
- Over 500 distinct protein modifications have been identified to date.
- Computational tools are increasingly vital for advancing the field.
- Significant progress is anticipated in discovering novel modifications and elucidating their biological roles.
Conclusions:
- The field of protein modifications has evolved significantly from early chemical analyses to modern high-throughput techniques.
- New computational approaches promise to revolutionize the discovery and functional characterization of protein modifications.
- Understanding protein modifications is critical for comprehending cellular biology.
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