Collidoscope: An Improved Tool for Computing Collisional Cross-Sections with the Trajectory Method
- 804 Downloads
Ion mobility-mass spectrometry (IM-MS) can be a powerful tool for determining structural information about ions in the gas phase, from small covalent analytes to large, native-like or denatured proteins and complexes. For large biomolecular ions, which may have a wide variety of possible gas-phase conformations and multiple charge sites, quantitative, physically explicit modeling of collisional cross sections (CCSs) for comparison to IMS data can be challenging and time-consuming. We present a “trajectory method” (TM) based CCS calculator, named “Collidoscope,” which utilizes parallel processing and optimized trajectory sampling, and implements both He and N2 as collision gas options. Also included is a charge-placement algorithm for determining probable charge site configurations for protonated protein ions given an input geometry in pdb file format. Results from Collidoscope are compared with those from the current state-of-the-art CCS simulation suite, IMoS. Collidoscope CCSs are within 4% of IMoS values for ions with masses from ~18 Da to ~800 kDa. Collidoscope CCSs using X-ray crystal geometries are typically within a few percent of IM-MS experimental values for ions with mass up to ~3.5 kDa (melittin), and discrepancies for larger ions up to ~800 kDa (GroEL) are attributed in large part to changes in ion structure during and after the electrospray process. Due to its physically explicit modeling of scattering, computational efficiency, and accuracy, Collidoscope can be a valuable tool for IM-MS research, especially for large biomolecular ions.
KeywordsIon mobility Native mass spectrometry Native IM-MS Collisional cross-section Computational theory Noncovalent complexes Trajectory method
Computations on the University of Oregon ACISS Supercomputing Cluster were supported by the National Science Foundation (grant OCI-0960354). The authors thank Elliott Ewing for helpful discussions.
- 5.Bernstein, S.L., Dupuis, N.F., Lazo, N.D., Wyttenbach, T., Condron, M.M., Bitan, G., Teplow, D.B., Shea, J.E., Ruotolo, B.T., Robinson, C.V., Bowers, M.T.: Amyloid-beta protein oligomerization and the importance of tetramers and dodecamers in the aetiology of Alzheimer's disease. Nat. Chem. 1, 326–331 (2009)CrossRefGoogle Scholar
- 14.Laganowsky, A., Reading, E., Allison, T.M., Ulmschneider, M.B., Degiacomi, M.T., Baldwin, A.J., Robinson, C.V.: Membrane proteins bind lipids selectively to modulate their structure and function. Nature 510, 172–175 (2014)Google Scholar
- 18.Campuzano, I., Bush, M.F., Robinson, C.V., Beaumont, C., Richardson, K., Kim, H., Kim, H.I.: Structural characterization of drug-like compounds by ion mobility mass spectrometry: comparison of theoretical and experimentally derived nitrogen collision cross sections. Anal. Chem. 84, 1026–1033 (2012)CrossRefGoogle Scholar
- 21.Salbo, R., Bush, M.F., Naver, H., Campuzano, I., Robinson, C.V., Pettersson, I., Jørgensen, T.J.D., Haselmann, K.F.: Traveling-wave ion mobility mass spectrometry of protein complexes: accurate calibrated collision cross-sections of human insulin oligomers. Rapid Commun. Mass Spectrom. 26, 1181–1193 (2012)CrossRefGoogle Scholar