Theoretical predictor for candidate structure assignment from IMS data of biomolecule-related conformational space
Emily R Schenk1, Frederic Nau1, Francisco Fernandez-Lima2
1Department of Chemistry and Biochemistry, Florida International University, Miami, FL 33199, USA.
International Journal for Ion Mobility Spectrometry : Official Publication of the International Society for Ion Mobility Spectrometry
|June 23, 2016
Summary
This study presents a computational workflow to link ion mobility experiments with theoretical models for biomolecule characterization. The method efficiently generates and assigns structures, aiding in the analysis of complex molecular conformations.
Area of Science:
- Biophysical Chemistry
- Computational Biology
- Structural Biology
Background:
- Correlating experimental ion mobility data with theoretical models is crucial for biomolecular characterization.
- Existing methods may lack efficiency or comprehensive structure assignment capabilities.
Purpose of the Study:
- To describe a theoretical workflow for generating and assigning candidate structures to experimental trapped ion mobility and H/D exchange mass spectrometry (HDX-TIMS-MS) data.
- To demonstrate the workflow's applicability for peptides and proteins with multiple conformations.
Main Methods:
- Utilizing molecular dynamics simulations and statistical filtering to generate candidate structures.
- Incorporating a "TIMS box" approach in molecular dynamics for improved sampling of intermediates in HDX-TIMS-MS experiments.
- Adapting the workflow for different ion mobility spectrometry (IMS) scenarios and collision cross-section (CCS) calculators.
Main Results:
- The described methodology offers a low computational cost and a simplified workflow.
- The workflow successfully illustrated its applicability for a peptide and protein example.
- The "TIMS box" molecular dynamics approach enhances sampling of molecular intermediates and local energy minima.
Conclusions:
- The developed theoretical workflow provides a powerful tool for correlating ion mobility data with structural models.
- The methodology is efficient, adaptable, and applicable to complex biomolecular systems.
- This approach facilitates a more accurate description of IMS experimental conditions and aids in structural elucidation.
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