Electrospray Surface Charge Describes Protein Molecular Motion

Chalk, R.; Borkowska, O.; Azeez, Kamal Abdul; Oerum, Stephanie; Born, Petra; Gileadi, O.; Burgess-Brown, N.

doi:10.1101/571091

Cited by 1 publication

(1 citation statement)

References 30 publications

(36 reference statements)

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“…These results suggest that contributions of long-range charge–dipole effects alone cannot account for the variation in CCS observed across individual protein ion native CSDs, consistent with previous findings . The inability of a single structure to explain the full range of experimental CCSs is also consistent with the hypothesis that protein ion CSDs arise from a distribution of multiple solution-phase folded states …”

Section: Resultssupporting

confidence: 90%

Investigation of Charge-State-Dependent Compaction of Protein Ions with Native Ion Mobility–Mass Spectrometry and Theory

Rolland

Biberic

Prell

2022

J. Am. Soc. Mass Spectrom.

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The precise relationship between native gas-phase protein ion structure, charge, desolvation, and activation remains elusive. Much evidence supports the Charge Residue Model for native protein ions formed by electrospray ionization, but scaling laws derived from it relate only to overall ion size. Closer examination of drift tube CCSs across individual native protein ion charge state distributions (CSDs) reveals deviations from global trends. To investigate whether this is due to structure variation across CSDs or contributions of long-range charge–dipole interactions, we performed in vacuo force field molecular dynamics (MD) simulations of multiple charge conformers of three proteins representing a variety of physical and structural features: β-lactoglobulin, concanavalin A, and glutamate dehydrogenase. Results from these simulated ions indicate subtle structure variation across their native CSDs, although effects of these structural differences and long-range charge-dependent interactions on CCS are small. The structure and CCS of smaller proteins may be more sensitive to charge due to their low surface-to-volume ratios and reduced capacity to compact. Secondary and higher order structure from condensed-phase structures is largely retained in these simulations, supporting the use of the term “native-like” to describe results from native ion mobility–mass spectrometry experiments, although, notably, the most compact structure can be the most different from the condensed-phase structure. Collapse of surface side chains to self-solvate through formation of new hydrogen bonds is a major feature of gas-phase compaction and likely occurs during the desolvation process. Results from these MD simulations provide new insight into the relationship of gas-phase protein ion structure, charge, and CCS.

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Section: Resultssupporting

confidence: 90%