Ion mobility-mass spectrometry applied to cyclic peptide analysis: Conformational preferences of gramicidin S and linear analogs in the gas phase

Ruotolo, Brandon T.; Tate, Colby C.; Russell, David H.

doi:10.1016/j.jasms.2004.02.006

Cited by 60 publications

(47 citation statements)

References 36 publications

(52 reference statements)

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“…By approximating the ion and buffer gas as hard spheres, the collision crosssection can be calculated from the mobility (K), temperature (T), pressure (P), number density (N*), masses of both the ion (m I ) and the buffer gas (m b ), and the charge of the ion (z): [17], where e is ionic charge and k B is Boltzmann's constant. The collision cross-sections reported herein were obtained using an internal calibration method [19]. Briefly, a peptide with a known cross-section (bradykinin) is used as the standard and the difference between the drift times of the standard and the ion of interest is measured multiple times and is used to calculate the ⍀ of the ion of interest relative to the standard.…”

Section: Experimental and Computational Methodsmentioning

confidence: 99%

The structure of gas-phase bradykinin fragment 1–5 (RPPGF) ions: An ion mobility spectrometry and H/D exchange ion-molecule reaction chemistry study

Sawyer

Marini

Stone

et al. 2005

J. Am. Soc. Mass Spectrom.

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Ion mobility-mass spectrometry (IM-MS) data is interpreted as evidence that gas-phase bradykinin fragment 1-5 (BK1-5, RPPGF) [M ϩ H] ϩ ions exist as three distinct structural forms, and the relative abundances of the structural forms depend on the solvent used to prepare the matrix-assisted laser desorption ionization (MALDI) samples. Samples prepared from organic rich solvents (90% methanol/10% water) yield ions having an ion mobility arrival-time distribution (ATD) that is dominated by a single peak; conversely, samples prepared using mostly aqueous solvents (10% methanol/90% water) yield an ATD composed of three distinct peaks. The BK1-5 [M ϩ H] ϩ ions were also studied by gas-phase hydrogen/deuterium (H/D) exchange ion-molecule reactions and this data supports our interpretation of the IM-MS data. Plausible structures for BK1-5 ions were generated by molecular dynamics (MD). Candidate MD-generated structures correlated to measured cross-sections suggest a compact conformer containing a ␤-turn whereas a more extended, open form does not contain such an interaction. This study illustrates the importance of intra-molecular interactions in the stabilization of the gas-phase ions, and these results clearly illustrate that solution-phase parameters (i.e., MALDI sample preparation) greatly influence the structures of gas-phase ions. tudies of peptide and protein structure play a major role in modern molecular biophysics and drive development of new, more specific and sensitive techniques. Gas-phase techniques for sequencing peptides and proteins are well established, and significant progress has been made in developing similar techniques for characterization of secondary (2°) and tertiary (3°) structures of gas-phase peptides/proteins [1][2][3][4][5]. Such studies increase our understanding of intra-molecular interactions and drive development of sequencing algorithms, but the relevance of gas-phase structure, structure in the absence of solvent [6], to solution-phase structure is still an open issue. The most important role of solvent is charge stabilization, and in the gas phase, charge stabilization occurs by intramolecular interactions [7]. Rapid progress is being made in the development of techniques that allow selective solvation (in terms of number of solvent molecules) of gas-phase peptide/protein ions [8], and these studies may serve to further our understanding of how solvent affects structure and function. In addition, gas-phase studies could enhance our understanding of intra-molecular interactions (i.e., hydrogen bonding, van der Waals interactions and hydrophobic forces), as well as how such interactions influence conformations in the solution phase or low dielectric environments (i.e., gas phase, membranes, and/or multimeric complexes).Bradykinin (amino acid sequence RPPGFSPR) has been extensively studied using both experimental and computational techniques. Bradykinin is an excellent model peptide for structural studies because the presence of arginine (R) at both the N-and C-terminus can potent...

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Section: Experimental and Computational Methodsmentioning

confidence: 99%

The structure of gas-phase bradykinin fragment 1–5 (RPPGF) ions: An ion mobility spectrometry and H/D exchange ion-molecule reaction chemistry study

Sawyer

Marini

Stone

et al. 2005

J. Am. Soc. Mass Spectrom.

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“…Energy determinations range in precision from force field-based relative energetics, for large systems, to density functional theory or ab initio approaches for smaller systems. Many varieties on this basic theme have appeared in the literature [7][8][9]17,42,[51][52][53][54][55][56][57][58][59] .…”

Section: How Is Molecular Modeling Employed To Analyze Data?mentioning

confidence: 99%

Ion mobility–mass spectrometry analysis of large protein complexes

et al. 2008

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Here we describe a detailed protocol for both data collection and interpretation with respect to ion mobility-mass spectrometry analysis of large protein assemblies. Ion mobility is a technique that can separate gaseous ions based on their size and shape. Specifically, within this protocol, we cover general approaches to data interpretation, methods of predicting whether specific model structures for a given protein assembly can be separated by ion mobility, and generalized strategies for data normalization and modeling. The protocol also covers basic instrument settings and best practices for both observation and detection of large noncovalent protein complexes by ion mobility-mass spectrometry. INTRODUCTIONLarge-scale interaction maps suggest a complex interplay of proteins within a myriad of functional assemblies 1,2 . A critical step in assigning functions to these assemblies is to determine their structure 3 . This goal is challenging, as many of these assemblies exist in low-copy numbers within cells, are frequently heterogeneous and may interact only transiently. Consequently, structural information for many protein complexes is not readily accessible by using the classical tools of structural biology (e.g., X-ray crystallography, nuclear magnetic resonance spectroscopy). New approaches are being developed that involve integrating data from a number of lower-resolution experimental methods and by combining distance and interaction restraints from these methods with homology modeling, architectural or even atomic models are being generated 4 . These restraints can be derived from a variety of experimental measurements including MS of intact complexes, chemical cross-linking, fluorescence resonance energy transfer, small angle X-ray scattering, and analytical ultracentrifugation 5,6 . One very recent addition to this series of biophysical tools is ion mobility separation coupled to mass spectrometry (IM-MS). IM is an established technique for studying shape and conformation in small molecules and individual proteins in the gas phase 7-10 but has only recently been applied to intact protein complexes 11,12 . When IM is coupled with MS, mass and consequently subunit composition can be determined simultaneously with the overall topology of protein complexes 10,12,13 .IM-MS analysis is performed by first ionizing the protein complex of interest. In our experiments, nano-electrospray ionization is used, typically requiring careful preparation procedures for most protein complexes. These procedures, as well as general practical aspects of sample preparation, are detailed in a protocol by Hernández and Robinson 14 . Although they are not discussed in detail here, knowledge of the materials and protocol steps described in that work are critical to the success of the protocol described below.After ionization, ions are injected into a region containing neutral gas at a controlled pressure (e.g., 0.5 mBar of nitrogen gas). Under the influence of a relatively weak electric field, injected ions undergo IM separation [7]...

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“…IM-MS enables the identification of unknowns through the determination of the mass-to-charge ratio as well as the collision cross section (size and shape) of an ion. This offers a number of benefits such as simplification of mass spectral data, separation of isomers and conformers, reduction in spectral noise and chemical interferences, chargestate separation and structure elucidation [57][58][59][60][61][62][63]. The evolution of IM-MS and applications of the technique have recently been reviewed by Hill et al [5].…”

Section: Quantitative Evaluationmentioning

confidence: 99%

Chemical standards for ion mobility spectrometry: a review

Kaur-Atwal

O’Connor

Aksenov

et al. 2009

Int. J. Ion Mobil. Spec.

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Ion mobility spectrometry (IMS), using standalone instrumentation and hyphenated with mass spectrometry (IM-MS), has recently undergone significant expansion in the numbers of users and applications, particularly in sectors outside its established user base; predominantly military and security applications. Although several IMS reference standards have been proposed, there are no currently universally recognised reference standards for the calibration and evaluation of mobility spectrometers. This review describes current practices and the literature on chemical standards for validating IMS systems in positive and negative ion modes. The key qualities and requirements an 'ideal' reference standard must possess are defined, together with the instrumental and environmental factors such as temperature, electric field, humidity and drift gas composition that may need to be considered. Important challenges that have yet to be resolved are also identified and proposals for future development presented.

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Ion mobility-mass spectrometry applied to cyclic peptide analysis: Conformational preferences of gramicidin S and linear analogs in the gas phase

Cited by 60 publications

References 36 publications

The structure of gas-phase bradykinin fragment 1–5 (RPPGF) ions: An ion mobility spectrometry and H/D exchange ion-molecule reaction chemistry study

The structure of gas-phase bradykinin fragment 1–5 (RPPGF) ions: An ion mobility spectrometry and H/D exchange ion-molecule reaction chemistry study

Ion mobility–mass spectrometry analysis of large protein complexes

Chemical standards for ion mobility spectrometry: a review

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