Compaction of RNA Hairpins and Their Kissing Complexes in Native Electrospray Mass Spectrometry

When electrosprayed from native solution conditions, RNA hairpins and kissing complexes acquire charge states at which they get significantly more compact in the gas phase than their initial structure in solution. Here we show the limits of using force field molecular dynamics to interpret the gas-phase structures of nucleic acid complexes in the gas phase, and we suggest that higher-level calculation levels should be used in the future.<br>

Download Full-text

Compaction of RNA Hairpins and Their Kissing Complexes in Native Electrospray Mass Spectrometry

10.26434/chemrxiv.11876505.v3 ◽

2020 ◽

Author(s):

Joséphine Abi-Ghanem ◽

Clémence Rabin ◽

Massimiliano Porrini ◽

Frédéric Rosu ◽

Valerie Gabelica

Keyword(s):

Mass Spectrometry ◽

Molecular Dynamics ◽

Gas Phase ◽

Electrospray Mass Spectrometry ◽

Initial Structure ◽

Phase Structures ◽

Native Ms ◽

Rna Hairpins ◽

Level Calculation ◽

Structure In Solution

When electrosprayed from typical native MS solution conditions, RNA hairpins and kissing complexes acquire charge states at which they get significantly more compact in the gas phase than their initial structure in solution. Here we show the limits of using force field molecular dynamics to interpret the gas-phase structures of nucleic acid complexes in the gas phase, and we suggest that higher-level calculation levels should be used in the future.<br>

Download Full-text

Compaction of RNA Hairpins and Their Kissing Complexes in Native Electrospray Mass Spectrometry

10.26434/chemrxiv.11876505 ◽

2020 ◽

Author(s):

Joséphine Abi-Ghanem ◽

Clémence Rabin ◽

Massimiliano Porrini ◽

Frédéric Rosu ◽

Valerie Gabelica

Keyword(s):

Mass Spectrometry ◽

Molecular Dynamics ◽

Gas Phase ◽

Electrospray Mass Spectrometry ◽

Initial Structure ◽

Phase Structures ◽

Native Ms ◽

Rna Hairpins ◽

Level Calculation ◽

Structure In Solution

When electrosprayed from typical native MS solution conditions, RNA hairpins and kissing complexes acquire charge states at which they get significantly more compact in the gas phase than their initial structure in solution. Here we show the limits of using force field molecular dynamics to interpret the gas-phase structures of nucleic acid complexes in the gas phase, and we suggest that higher-level calculation levels should be used in the future.<br>

Download Full-text

Compaction of Duplex Nucleic Acids upon Native Electrospray Mass Spectrometry

10.1101/105049 ◽

2017 ◽

Author(s):

Massimiliano Porrini ◽

Frédéric Rosu ◽

Clémence Rabin ◽

Leonardo Darré ◽

Hansel Gómez ◽

...

Keyword(s):

Mass Spectrometry ◽

Molecular Dynamics ◽

Nucleic Acids ◽

Gas Phase ◽

Density Functional ◽

Native Mass Spectrometry ◽

Native Solution ◽

Solution Structures ◽

Dna And Rna ◽

Charge States

ABSTRACTNative mass spectrometry coupled to ion mobility spectrometry is a promising tool for structural biology. Intact complexes can be transferred to the mass spectrometer and, if native conformations survive, collision cross sections give precious information on the structure of each species in solution. Based on several successful reports for proteins and their complexes, the conformation survival becomes more and more taken for granted. Here we report on the fate of nucleic acids conformation in the gas phase. Disturbingly, we found that DNA and RNA duplexes, at the electrospray charge states naturally obtained from native solution conditions (≥ 100 mM aqueous NH4OAc), are significantly more compact in the gas phase compared to the canonical solution structures. The compaction is observed for short (12-bp) and long (36-bp) duplexes, and for DNA and RNA alike. Molecular modeling (density functional calculations on small helices, semi-empirical calculations on up to 12-bp, and molecular dynamics on up to 36-bp duplexes) demonstrates that the compaction is due to phosphate group self-solvation prevailing over Coulomb-driven expansion. Molecular dynamics simulations starting from solution structures do not reproduce the experimental compaction. To be experimentally relevant, molecular dynamics sampling should reflect the progressive structural rearrangements occurring during desolvation. For nucleic acid duplexes, the compaction observed for low charge states results from novel phosphate-phosphate hydrogen bonds formed across both grooves at the very late stages of electrospray.

Download Full-text

Deprotonated carbohydrate anion fragmentation chemistry: structural evidence from tandem mass spectrometry, infra-red spectroscopy, and theory

Physical Chemistry Chemical Physics ◽

10.1039/c8cp02620c ◽

2018 ◽

Vol 20 (44) ◽

pp. 27897-27909 ◽

Cited By ~ 7

Author(s):

Jordan M. Rabus ◽

Daniel R. Simmons ◽

Philippe Maître ◽

Benjamin J. Bythell

Keyword(s):

Mass Spectrometry ◽

Infrared Spectroscopy ◽

Tandem Mass Spectrometry ◽

Gas Phase ◽

Tandem Mass ◽

Phase Structures ◽

Infra Red ◽

Fragmentation Chemistry

We investigate the gas-phase structures and fragmentation chemistry of deprotonated carbohydrate anions using combined tandem mass spectrometry, infrared spectroscopy, regioselective labelling, and theory.

Download Full-text

Gas-Phase Structure of the Histone Multimers Characterized by Ion Mobility Mass Spectrometry and Molecular Dynamics Simulation

Analytical Chemistry ◽

10.1021/ac400395j ◽

2013 ◽

Vol 85 (8) ◽

pp. 4165-4171 ◽

Cited By ~ 18

Author(s):

Kazumi Saikusa ◽

Sotaro Fuchigami ◽

Kyohei Takahashi ◽

Yuuki Asano ◽

Aritaka Nagadoi ◽

...

Keyword(s):

Mass Spectrometry ◽

Molecular Dynamics ◽

Molecular Dynamics Simulation ◽

Gas Phase ◽

Ion Mobility ◽

Phase Structure ◽

Dynamics Simulation ◽

Ion Mobility Mass Spectrometry ◽

Gas Phase Structure

Download Full-text

Gas-Phase Fragmentation Studies of Biotinylated, Hexaethylene Glycol–Spacered Oligosaccharides—Molecular Probes—Using Electrospray Mass Spectrometry on a Hybrid High-Resolution Mass Spectrometer

Journal of Analytical Chemistry ◽

10.1134/s1061934817130044 ◽

2017 ◽

Vol 72 (13) ◽

pp. 1312-1321

Author(s):

A. O. Chizhov ◽

D. A. Argunov ◽

M. L. Gening ◽

E. V. Sukhova ◽

E. A. Khatuntseva ◽

...

Keyword(s):

Mass Spectrometry ◽

High Resolution ◽

Gas Phase ◽

Mass Spectrometer ◽

Electrospray Mass Spectrometry ◽

Molecular Probes ◽

High Resolution Mass ◽

Gas Phase Fragmentation ◽

High Resolution Mass Spectrometer ◽

Resolution Mass

Download Full-text

Mass Spectrometric Analysis of Antibody—Epitope Peptide Complex Dissociation: Theoretical Concept and Practical Procedure of Binding Strength Characterization

Molecules ◽

10.3390/molecules25204776 ◽

2020 ◽

Vol 25 (20) ◽

pp. 4776

Author(s):

Bright D. Danquah ◽

Kwabena F. M. Opuni ◽

Claudia Roewer ◽

Cornelia Koy ◽

Michael O. Glocker

Keyword(s):

Mass Spectrometry ◽

Dissociation Constant ◽

Gas Phase ◽

Immune Complex ◽

Room Temperature ◽

Electrospray Mass Spectrometry ◽

Small Sample ◽

Epitope Peptide ◽

Ligand Complex ◽

Dissociation Constant Kd

Electrospray mass spectrometry is applied to determine apparent binding energies and quasi equilibrium dissociation constants of immune complex dissociation reactions in the gas phase. Myoglobin, a natural protein-ligand complex, has been used to develop the procedure which starts from determining mean charge states and normalized and averaged ion intensities. The apparent dissociation constant KD m0g#= 3.60 × 10−12 for the gas phase heme dissociation process was calculated from the mass spectrometry data and by subsequent extrapolation to room temperature to mimic collision conditions for neutral and resting myoglobin. Similarly, for RNAse S dissociation at room temperature a KD m0g#= 4.03 × 10−12 was determined. The protocol was tested with two immune complexes consisting of epitope peptides and monoclonal antibodies. For the epitope peptide dissociation reaction of the FLAG peptide from the antiFLAG antibody complex an apparent gas phase dissociation constant KD m0g#= 4.04 × 10−12 was calculated. Likewise, an apparent KD m0g#= 4.58 × 10−12 was calculated for the troponin I epitope peptide—antiTroponin I antibody immune complex dissociation. Electrospray mass spectrometry is a rapid method, which requires small sample amounts for either identification of protein-bound ligands or for determination of the apparent gas phase protein-ligand complex binding strengths.

Download Full-text