NP³ MS Workflow: An Open-Source Software System to Empower Natural Product-Based Drug Discovery Using Untargeted...

Area of Science:

• * Chemistry and Biology Interface
• * Drug Discovery and Development
• * Natural Product Research

Background:

• * Natural products are a primary source of new drugs.
• * Current drug discovery requires high-throughput methods incompatible with traditional natural product research.
• * There is a need for efficient tools to analyze complex natural product mixtures.

Purpose of the Study:

• * Introduce the NP3 MS Workflow, an open-source software for analyzing untargeted metabolomic data.
• * Enable direct ranking of bioactive natural products from complex mixtures.
• * Facilitate integration into natural product-based drug discovery pipelines.

Main Methods:

• * Development of a robust open-source software system for liquid chromatography-tandem mass spectrometry (LC-MS/MS) data processing.
• * Implementation of minimal user intervention with customizable LC-MS/MS data processing steps.
• * Incorporation of diagnostic statistics for data interpretation and optimization.
• * Advanced computation of MS2 spectra, automatic ion deconvolution, structural annotation, and precursor ion quantification.

Main Results:

• * NP3 MS Workflow enables efficient analysis and ranking of bioactive natural products from complex mixtures.
• * The software provides improved MS2 spectra computation and automatic deconvolution using fragmentation rules.
• * Tools for structural annotation against MS2 databases and relative quantification for bioactivity correlation are included.
• * Case studies and comparisons demonstrate the software's robustness and utility.

Conclusions:

• * NP3 MS Workflow offers a robust and useful approach for selecting bioactive natural products from complex samples.
• * The software enhances the toolkit for untargeted metabolomics.
• * It can be readily integrated into natural product drug discovery and other chemistry-biology research fields.