Collidoscope: An Improved Tool for Computing Collisional Cross-Sections with the Trajectory Method.

Area of Science:

• Physical Chemistry
• Biophysical Techniques
• Computational Chemistry

Background:

• Ion mobility-mass spectrometry (IM-MS) provides structural insights into gas-phase ions, including large biomolecules.
• Accurate modeling of collisional cross sections (CCSs) for large biomolecular ions is challenging due to conformational complexity and multiple charge sites.
• Existing methods for CCS calculation can be time-consuming and computationally intensive.

Purpose of the Study:

• To introduce Collidoscope, a novel trajectory method-based CCS calculator designed for efficient and accurate modeling of ion structures.
• To provide a tool that aids in the interpretation of IM-MS data, particularly for large and complex biomolecular ions.
• To develop a charge-placement algorithm for predicting probable charge configurations on protonated protein ions.

Main Methods:

• Development of the Collidoscope software, employing parallel processing and optimized trajectory sampling for CCS calculations.
• Implementation of He and N2 as collision gas options within the Collidoscope framework.
• Integration of a charge-placement algorithm utilizing PDB input geometries for protein ions.

Main Results:

• Collidoscope demonstrates high accuracy, with CCS values within 4% of the state-of-the-art IMoS suite for ions ranging from 18 Da to 800 kDa.
• For ions up to 3.5 kDa, Collidoscope CCSs derived from X-ray crystal structures show agreement within a few percent of experimental IM-MS data.
• Discrepancies for larger ions (up to 800 kDa) are largely attributed to structural changes occurring during the electrospray process.

Conclusions:

• Collidoscope offers a computationally efficient and accurate method for calculating CCSs, valuable for IM-MS research.
• The software's physically explicit modeling of scattering enhances its utility for analyzing complex ion structures.
• Collidoscope is particularly beneficial for studies involving large biomolecular ions, bridging simulation and experimental data.