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Fragmentation Spectra Prediction and DNA Adducts Structural Determination
Andrea Carrà1, Veronica Macaluso2, Peter W Villalta1
1Masonic Cancer Center, University of Minnesota, 2231 6th Street SE, Minneapolis, MN, 55455, USA.
Journal of the American Society for Mass Spectrometry
|November 8, 2019
Summary
Chemical dynamics simulations predict DNA adduct fragmentation mass spectra for structural determination. Considering tautomers is key for accurate theoretical spectra, aiding in identifying reaction pathways and product structures.
Area of Science:
- Computational chemistry
- Mass spectrometry
- Molecular dynamics
Background:
- DNA adducts are critical in toxicology and carcinogenesis.
- Accurate structural determination of DNA adducts is essential for understanding their biological impact.
- Existing methods for DNA adduct identification can be limited in scope and accuracy.
Purpose of the Study:
- To optimize chemical dynamics simulations for predicting DNA adduct fragmentation mass spectra.
- To establish a protocol for structural determination of DNA adducts using theoretical spectra.
- To compare first principles simulations with machine learning models for fragmentation analysis.
Main Methods:
- Utilized chemical dynamics simulations to calculate theoretical fragmentation mass spectra.
- Employed O6-methylguanine (O6-Me-G) as a model DNA adduct.
- Developed an automatic protocol to incorporate tautomerization during simulations.
- Compared theoretical results with experimental high-resolution fragmentation data.
Main Results:
- Predicted fragmentation mass spectra for O6-Me-G showed good agreement with experimental data.
- The inclusion of tautomers significantly improved the completeness of theoretical spectra.
- Identified reaction pathways and product structures by analyzing simulated fragmentation patterns.
- Demonstrated the applicability of a mobile proton model to nucleobase fragmentation.
Conclusions:
- Chemical dynamics simulations are effective for DNA adduct structural determination.
- Tautomerization is a critical factor in accurately modeling DNA adduct fragmentation.
- The developed computational approach aids in identifying unknown DNA adducts and their properties.
- This study provides a foundation for integrating advanced computational methods in DNA damage analysis.
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