Exploring the Impacts of Conformer Selection Methods on Ion Mobility Collision Cross Section Predictions

Area of Science:

• Computational Chemistry
• Molecular Modeling
• Spectrometry

Background:

• Accurate prediction of structure-dependent molecular properties is essential for fields like ion mobility spectrometry.
• The reliability of these predictions hinges on selecting appropriate molecular conformer populations.
• Existing conformation selection methods vary in their effectiveness and computational demands.

Purpose of the Study:

• To conduct a comprehensive evaluation of various conformation selection techniques for molecular property prediction.
• To assess the impact of different selection strategies on the accuracy and computational cost of predicting collision cross sections.
• To identify optimal methods for selecting molecular conformers in computational chemistry workflows.

Main Methods:

• Generated 50,000 conformers for 18 molecules using the In Silico Chemical Library Engine (ISiCLE).
• Employed Monte Carlo simulations to analyze conformer variability and evaluate selection techniques (averaging, Boltzmann weighting, energy thresholds, similarity reduction).
• Calculated ion mobility collision cross sections for all generated conformers.

Main Results:

• Boltzmann weighting demonstrated a favorable balance between predictive precision and theoretical accuracy.
• Combining energy thresholds and root-mean-squared deviation-based similarity reduction significantly reduced computational costs while preserving accuracy.
• Molecular dynamics simulations (e.g., AMBER) can yield new low-energy conformers over extended runs, impacting precision.

Conclusions:

• Boltzmann weighting is a robust method for conformer selection, offering a good compromise between accuracy and efficiency.
• Hybrid approaches, integrating energy and similarity criteria, enhance computational efficiency without sacrificing predictive accuracy.
• Density functional theory geometry optimization on selected conformers can further improve precision and theoretical accuracy, especially when dealing with extensive conformer sets.