ModiFinder: Tandem Mass Spectral Alignment Enables Structural Modification Site Localization

Area of Science:

• Analytical Chemistry
• Computational Chemistry
• Metabolomics

Background:

• Untargeted tandem mass spectrometry (MS/MS) is a high-throughput method for small molecule analysis.
• Computational methods like MS/MS library search, analog library search, and molecular networking aid in compound identification.
• Automated methods for site-specific structural modification information in MS/MS data are lacking.

Purpose of the Study:

• To introduce ModiFinder, a novel computational tool for localizing structural modifications in small molecules.
• To leverage MS/MS spectral peak alignment between known and unknown compounds to identify modification sites.
• To enhance the capabilities of MS/MS analog searching and molecular networking for novel compound discovery.

Main Methods:

• ModiFinder aligns MS/MS spectra of structurally related known and unknown small molecules.
• It focuses on shifted MS/MS fragment peaks to identify substructures containing modifications.
• The tool synthesizes peak alignment information to score the likelihood of modification sites on known molecules.

Main Results:

• ModiFinder effectively localizes structural modifications in small molecules.
• The method enhances the identification of unknown compounds by pinpointing modification sites.
• Demonstrated utility in accelerating the discovery of novel chemical entities.

Conclusions:

• ModiFinder provides site-specific information on structural modifications, a previously unmet need in MS/MS data analysis.
• This tool significantly advances the capabilities of analog searching and molecular networking.
• ModiFinder is poised to accelerate the discovery of novel compounds through improved structural elucidation.