Strengths and Weaknesses of Molecular Simulations of Electrosprayed Droplets

Consta, Styliani; Oh, Myong In; Kwan, Victor; Malevanets, Anatoly

doi:10.1007/s13361-018-2039-2

Cited by 19 publications

(25 citation statements)

References 82 publications

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“…Combining these approaches with structural "fingerprinting" via collision-induced unfolding [14] as well as with H/D exchange experiments [50], novel dissociation methods [91], ion spectroscopy [12,92], and other experimental methods should provide yet more structural constraints for MD simulations. The recent inclusion of nanoscale water droplet environments [45,75] and mobile charges [36] in MD simulations represents a step forward in realism, and more accurate parametrization of water models for nanoscale droplets is expected to provide unparalleled insight into native ion compaction and structure.…”

Section: Discussionmentioning

confidence: 99%

“…During the last decade or so, efforts to accurately simulate desiccation of biomolecules within ESI droplets and concomitant acquisition of charge have been undertaken by several groups [36,37,44,45,51,67,[74][75][76][77]. In addition to the aforementioned simulations by Steinberg et al [48], the Konermann and Consta groups have applied MD simulations to charged droplets containing biomolecules to learn about ionization mechanisms, ion compaction upon desiccation, and heating-induced unfolding and dissociation.…”

Section: Explicit Modeling Of Nesi Droplet Evaporation and Ion Chargimentioning

confidence: 99%

“…These computations can be especially sensitive to choice of water model, treatment of electrostatics, temperature control, and simulation length, among other user-determined variables [51]. These simulations provide insight into native charge distributions of proteins and protein complexes produced by nESI [44], droplet evaporation dynamics [75][76][77], as well as the role of charge hopping and charge-charge repulsion in both the ionization and collision-induced dissociation processes [36].…”

Section: Explicit Modeling Of Nesi Droplet Evaporation and Ion Chargimentioning

confidence: 99%

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Computational insights into compaction of gas-phase protein and protein complex ions in native ion mobility-mass spectrometry

Rolland

Prell

2019

TrAC Trends in Analytical Chemistry

103

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Native ion mobility-mass spectrometry (IM-MS) is a rapidly growing field for studying the composition and structure of biomolecules and biomolecular complexes using gas-phase methods. Typically, ions are formed in native IM-MS using gentle nanoelectrospray ionization conditions, which in many cases can preserve condensed-phase stoichiometry. Although much evidence shows that large-scale condensed-phase structure, such as quaternary structure and topology, can also be preserved, it is less clear to what extent smaller-scale structure is preserved in native IM-MS. This review surveys computational and experimental efforts aimed at characterizing compaction and structural rearrangements of protein and protein complex ions upon transfer to the gas phase. A brief summary of gas-phase compaction results from molecular dynamics simulations using multiple common force fields and a wide variety of protein ions is presented and compared to literature IM-MS data.

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Section: Discussionmentioning

confidence: 99%

Section: Explicit Modeling Of Nesi Droplet Evaporation and Ion Chargimentioning

confidence: 99%

Section: Explicit Modeling Of Nesi Droplet Evaporation and Ion Chargimentioning

confidence: 99%

See 1 more Smart Citation

Computational insights into compaction of gas-phase protein and protein complex ions in native ion mobility-mass spectrometry

Rolland

Prell

2019

TrAC Trends in Analytical Chemistry

103

View full text Add to dashboard Cite

show abstract

“…We without the use of a laser, can aid in obtaining the fundamental knowledge necessary for developing a predictive model of the ionization processes, similar to work on ESI and MALDI. [151][152][153] The new ionization processes eliminate the need, in the traditional sense, for an 'ion source' with associated cost and user expertise or potential danger related to high voltages, a laser, or even heat. The detection limit of vMAI using 3-NBN matrix was 7 amol of fexofenadine on a dedicated source that is also ultimately robust allowing 1 mmol of analyte, as previously shown, 51 to be acquired without carryover, while also being exceptionally simple.…”

Section: Discussionmentioning

confidence: 99%

“…Multi‐ionization methods in a dedicated single platform provide improved information content vs any single ionization method used in MS. Dedicated sources, with and without the use of a laser, can aid in obtaining the fundamental knowledge necessary for developing a predictive model of the ionization processes, similar to work on ESI and MALDI 151–153 . The new ionization processes eliminate the need, in the traditional sense, for an ‘ion source’ with associated cost and user expertise or potential danger related to high voltages, a laser, or even heat.…”

Section: Discussionmentioning

confidence: 99%

An overview of biological applications and fundamentals of new inlet and vacuum ionization technologies

Trimpin

Marshall

Karki

et al. 2020

Rapid Comm Mass Spectrometry

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Rationale The developments of new ionization technologies based on processes previously unknown to mass spectrometry (MS) have gained significant momentum. Herein we address the importance of understanding these unique ionization processes, demonstrate the new capabilities currently unmet by other methods, and outline their considerable analytical potential. Methods The inlet and vacuum ionization methods of solvent‐assisted ionization (SAI), matrix‐assisted ionization (MAI), and laserspray ionization can be used with commercial and dedicated ion sources producing ions from atmospheric or vacuum conditions for analyses of a variety of materials including drugs, lipids, and proteins introduced from well plates, pipet tips and plate surfaces with and without a laser using solid or solvent matrices. Mass spectrometers from various vendors are employed. Results Results are presented highlighting strengths relative to ionization methods of electrospray ionization (ESI) and matrix‐assisted laser desorption/ionization. We demonstrate the utility of multi‐ionization platforms encompassing MAI, SAI, and ESI and enabling detection of what otherwise is missed, especially when directly analyzing mixtures. Unmatched robustness is achieved with dedicated vacuum MAI sources with mechanical introduction of the sample to the sub‐atmospheric pressure (vacuum MAI). Simplicity and use of a wide array of matrices are attained using a conduit (inlet ionization), preferably heated, with sample introduction from atmospheric pressure. Tissue, whole blood, urine (including mouse, chicken, and human origin), bacteria strains and chemical on‐probe reactions are analyzed directly and, especially in the case of vacuum ionization, without concern of carryover or instrument contamination. Conclusions Examples are provided highlighting the exceptional analytical capabilities associated with the novel ionization processes in MS that reduce operational complexity while increasing speed and robustness, achieving mass spectra with low background for improved sensitivity, suggesting the potential of this simple ionization technology to drive MS into areas currently underserved, such as clinical and medical applications.

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Inter-Domain Repulsion of Dumbbell-Shaped Calmodulin during Electrospray Ionization Revealed by Molecular Dynamics Simulations

et al. 2023

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The mechanisms whereby protein ions are released from nanodroplets at the liquid–gas interface have continued to be controversial since electrospray ionization (ESI) mass spectrometry was widely applied in biomolecular structure analysis in solution. Several viable pathways have been proposed and verified for single-domain proteins. However, the ESI mechanism of multi-domain proteins with more complicated and flexible structures remains unclear. Herein, dumbbell-shaped calmodulin was chosen as a multi-domain protein model to perform molecular dynamics simulations to investigate the structural evolution during the ESI process. For [Ca4CAM], the protein followed the classical charge residue model. As the inter-domain electrostatic repulsion increased, the droplet was found to split into two sub-droplets, while stronger-repulsive apo-calmodulin unfolded during the early evaporation stage. We designated this novel ESI mechanism as the domain repulsion model, which provides new mechanistic insights into further exploration of proteins containing more domains. Our results suggest that greater attention should be paid to the effect of domain–domain interactions on structure retention during liquid–gas interface transfer when mass spectrometry is used as the developing technique in gas phase structural biology.

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Strengths and Weaknesses of Molecular Simulations of Electrosprayed Droplets

Cited by 19 publications

References 82 publications

Computational insights into compaction of gas-phase protein and protein complex ions in native ion mobility-mass spectrometry

Computational insights into compaction of gas-phase protein and protein complex ions in native ion mobility-mass spectrometry

An overview of biological applications and fundamentals of new inlet and vacuum ionization technologies

Inter-Domain Repulsion of Dumbbell-Shaped Calmodulin during Electrospray Ionization Revealed by Molecular Dynamics Simulations

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