Determining the properties of gas-phase clusters

Hopkins, W. Scott

doi:10.1080/00268976.2015.1053545

Cited by 24 publications

(33 citation statements)

References 64 publications

(114 reference statements)

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“…The changes in the mobility profile observed for cyt C and Mb in the presence of gas‐phase modifiers suggests that the protein molecular ions are clustering with the modifier gas molecules while trapped in the TIMS cell. It is known that transient ionic clusters can be formed from modifiers in the bath gas/drift gas and analyte ions generated by ESI . The nature of the gas‐phase modifiers suggests that the main interactions which stabilize site‐specific modifier adsorption and cluster formation are based on ion‐dipole or dipole–dipole interactions between the modifier and ionized or polar amino acid residues exposed on the protein surface.…”

Section: Resultssupporting

confidence: 93%

“…for lower-mobility bands in the presence of modifiers, particularly for the +6 to +7 charge states of cyt C and the +7 to +8 charge states of * denotes apoprotein signals generated by ESI. 30 The nature of the gas-phase modifiers suggests that the main interactions which stabilize site-specific modifier adsorption and cluster formation are based on ion-dipole or dipole-dipole interactions between the modifier and ionized or polar amino acid residues exposed on the protein surface. All gas-phase modifiers used in this study have dipole moments similar to or higher than that of water (i.e., 1.70 D for MeOH, 3.92 D for ACN, and 2.69 D for acetone), favoring clustering in the gas phase.…”

Section: Mobility Profiles Of Cyt C Show Increased Relative Abundancementioning

confidence: 99%

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The effects of solution additives and gas‐phase modifiers on the molecular environment and conformational space of common heme proteins

Butcher

Mikšovská

Ridgeway

et al. 2019

Rapid Comm Mass Spectrometry

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Rationale The molecular environment is known to impact the secondary and tertiary structures of biomolecules both in solution and in the gas phase, shifting the equilibrium between different conformational and oligomerization states. However, there is a lack of studies monitoring the impacts of solution additives and gas‐phase modifiers on biomolecules characterized using ion mobility techniques. Methods The effect of solution additives and gas‐phase modifiers on the molecular environment of two common heme proteins, bovine cytochrome c and equine myoglobin, is investigated as a function of the time after desolvation (e.g., 100–500 ms) using nanoelectrospray ionization coupled to trapped ion mobility spectrometry with detection by time‐of‐flight mass spectrometry. Organic compounds used as additives/modifiers (methanol, acetonitrile, acetone) were either added to the aqueous protein solution before ionization or added to the ion mobility bath gas by nebulization. Results Changes in the mobility profiles are observed depending on the starting solution composition (i.e., in aqueous solution at neutral pH or in the presence of organic content: methanol, acetone, or acetonitrile) and the protein. In the presence of gas‐phase modifiers (i.e., N2 doped with methanol, acetone, or acetonitrile), a shift in the mobility profiles driven by the gas‐modifier mass and size and changes in the relative abundances and number of IMS bands are observed. Conclusions We attribute the observed changes in the mobility profiles in the presence of gas‐phase modifiers to a clustering/declustering mechanism by which organic molecules adsorb to the protein ion surface and lower energetic barriers for interconversion between conformational states, thus redefining the free energy landscape and equilibria between conformers. These structural biology experiments open new avenues for manipulation and interrogation of biomolecules in the gas phase with the potential to emulate a large suite of solution conditions, ultimately including conditions that more accurately reflect a variety of intracellular environments.

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Section: Resultssupporting

confidence: 93%

Section: Mobility Profiles Of Cyt C Show Increased Relative Abundancementioning

confidence: 99%

The effects of solution additives and gas‐phase modifiers on the molecular environment and conformational space of common heme proteins

Butcher

Mikšovská

Ridgeway

et al. 2019

Rapid Comm Mass Spectrometry

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“…However, differential mobility spectrometry (DMS) has recently shown promise in this regard 2 – 4 . Most commonly employed as a narrow-pass filter to separate ions from chemical noise 5 , 6 , DMS takes advantage of an oscillating asymmetric electric field to drive rapid cycles of microsolvation and evaporation in environments that are seeded with low partial pressures of solvent vapor 3 , 7 , 8 . In examining how ion microsolvation properties are affected by specific structural attributes, the influence of electronic and resonance effects 2 , 9 , the steric hindrance of charge sites 2 , 10 , 11 , and the influence of intramolecular hydrogen bonding have been observed 12 .…”

Section: Introductionmentioning

confidence: 99%

Determining molecular properties with differential mobility spectrometry and machine learning

et al. 2018

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The fast and accurate determination of molecular properties is highly desirable for many facets of chemical research, particularly in drug discovery where pre-clinical assays play an important role in paring down large sets of drug candidates. Here, we present the use of supervised machine learning to treat differential mobility spectrometry – mass spectrometry data for ten topological classes of drug candidates. We demonstrate that the gas-phase clustering behavior probed in our experiments can be used to predict the candidates’ condensed phase molecular properties, such as cell permeability, solubility, polar surface area, and water/octanol distribution coefficient. All of these measurements are performed in minutes and require mere nanograms of each drug examined. Moreover, by tuning gas temperature within the differential mobility spectrometer, one can fine tune the extent of ion-solvent clustering to separate subtly different molecular geometries and to discriminate molecules of very similar physicochemical properties.

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“…The changes in the mobility profile observed for cyt C and Mb in the presence of gasphase modifiers suggests that the protein molecular ions are clustering with the modifier gas molecules while trapped in the TIMS cell. It is known that transient ionic clusters can be formed from modifiers in the bath gas/drift gas and analyte ions generated by electrospray ionization 22 .…”

Section: Mobility Profiles Of Cyt C Show Increased Relative Abundancementioning

confidence: 99%

Solution and gas-phase modifiers effect on heme proteins environment and conformational space

Butcher

Mikšovská

Ridgeway

et al. 2018

Preprint

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The molecular environment is known to impact the secondary and tertiary structure of biomolecules, shifting the equilibrium between different conformational and oligomerization states. In the present study, the effect of solution additives and gas-phase modifiers on the molecular environment of two common heme proteins, bovine cytochrome c and equine myoglobin, is investigated as a function of the time after desolvation (e.g., 100 -500 ms) using trapped ion mobility spectrometrymass spectrometry. Changes in the mobility profiles are observed depending on the starting solution composition (i.e., in aqueous solution at neutral pH or in the presence of organic content: methanol, acetone, or acetonitrile) depending on the protein. In the presence of gas-phase modifiers (i.e., N 2 containing methanol, acetone, or acetonitrile), a shift in the mobility profiles driven by the gas-modifier mass and size and changes in the relative abundances and number of IMS bands are observed. We attribute these changes in the mobility profiles in the presence of gas-phase modifiers to a clustering/declustering mechanism by which organic molecules adsorb to the protein ion surface and lower energetic barriers for interconversion between conformational states, thus redefining the free energy landscape and equilibria between conformers. These structural biology experiments open new avenues for manipulation and interrogation of biomolecules in the gasphase with the potential to emulate a large suite of solution conditions, ultimately including conditions that more accurately reflect a variety of intracellular environments.

show abstract

Determining the properties of gas-phase clusters

Cited by 24 publications

References 64 publications

The effects of solution additives and gas‐phase modifiers on the molecular environment and conformational space of common heme proteins

The effects of solution additives and gas‐phase modifiers on the molecular environment and conformational space of common heme proteins

Determining molecular properties with differential mobility spectrometry and machine learning

Solution and gas-phase modifiers effect on heme proteins environment and conformational space

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