Linking molecular models with ion mobility experiments. Illustration with a rigid nucleic acid structure

Area of Science:

• Analytical Chemistry
• Structural Biology
• Computational Chemistry

Background:

• Ion mobility spectrometry (IMS) provides experimental collision cross sections (Ω(EXP)) for ions.
• Molecular modeling complements IMS by calculating theoretical collision cross sections (Ω(CALC)) for proposed ion structures.
• Comparing Ω(EXP) and Ω(CALC)) is crucial for determining compatible ion 3D structures.

Purpose of the Study:

• To address key questions for applying IMS to new molecular systems, particularly nucleic acids.
• To investigate experimental error in Ω(EXP) determination, especially with traveling wave ion guide calibration.
• To guide the generation of plausible gas-phase 3D models and selection of appropriate Ω(CALC) calculation methods.

Main Methods:

• Utilized a known rigid structure, the tetramolecular G-quadruplex [dTGGGGT]4, as a model system.
• Explored methods for estimating experimental error in collision cross section measurements.
• Investigated strategies for generating 3D molecular models and calculating their collision cross sections.

Main Results:

• Presented a detailed tutorial framework for applying IMS to structural characterization.
• Provided insights into the challenges and solutions for applying IMS to novel molecular systems.
• Demonstrated the utility of a well-defined G-quadruplex structure for validating IMS methodologies.

Conclusions:

• Ion mobility spectrometry, coupled with molecular modeling, is a powerful tool for structural elucidation.
• This work offers practical guidance for researchers applying IMS to complex molecules like nucleic acids.
• The study highlights the importance of understanding experimental parameters and computational models for accurate structural determination.