Resolving the Discrepancies Between Empirical and Rayleigh Charge Limiting Models for Globular Proteins

Abstract

Starting with the Rayleigh charge limiting model, a slightly different approach is used to account for the well-known discrepancy that exists between the said model and experimental ESI MS data for globular proteins. It is shown using published datasets that for globular proteins, the mass density ρ exhibits a weak second-order dependence on its mass M, according to ρ(M)∝ M, α ~ 0.14. A direct equivalence established between ESI MS and x-ray techniques suggests a minimum but critical surface tension of 15.6 ± 5.2 mN/m for the droplet at the liquid-to-gas phase transition point. The packing density factor η for globular proteins is believed to lie between 1 (very tightly packed) and 4.6 (less tight, natively packed). While the Rayleigh charge limiting model has been linked historically to the CRM (J. Chem. Phys. 49:2240-2249, 1968; Anal. Chim. Acta 406:93-104, 2000), this paper does not expressly seek to justify the CRM, but rather uses empirical data and existing knowledge across subfields to help build a consistent picture of ESI MS phenomena that might be difficult to explain otherwise. These results would be useful in molecular dynamics (MD) simulations, understanding liquid-to-gas phase transitions and in opening up new routes for cross-calibration between ESI MS, IM MS, NMR and x-ray crystallography studies. Graphical Abstract ᅟ.

Observation of Magic Number Clusters from Thermal Dissociation Molecular Dynamics Simulations of Lithium Formate Ionic Clusters

“…While the basic principles and mechanisms for the formation of these ions are understood, the particular mechanism depends upon certain details of the ions. The charged residue model (CRM) predicts that the detected ions are formed from the evaporation of the solvent. − By contrast, the ion evaporation model (IEM) − is consistent with the ejection of small groups (<10) of small ions from the surface of the droplet . There does appear to be examples wherein the mechanismIEM versus CRMis not clearly elucidated, , and there are even hybrid models that include both. − …”

Ion Mobility Mass Spectrometry Measures the Conformational Landscape of p27 and its Domains and how this is Modulated upon Interaction with Cdk2/cyclin A

“…[8] The value of Z R is known to deviate for proteins that are not inherently globular and maybe over-estimated for proteins with molecular weights below 100 kDa. [9] Focusing on the p27-C domain first, MS analysis reveals a broad charge state distribution Δz =11 where 6 ≤ z ≤17, with most intensity in the lowest two charge states, [M+6H] 6+ and [M+7H] 7+ (Figure 2b). Such a charge state distribution is indicative of a protein that contains both compact (perhaps structured) as well as extended regions.…”