Surface-Induced Dissociation of Noncovalent Protein Complexes in an Extended Mass Range Orbitrap Mass Spectrometer

2018 ◽  
Author(s):  
Zachary VanAernum ◽  
Joshua D. Gilbert ◽  
Mikhail E. Belov ◽  
Alexander A. Makarov ◽  
Stevan R. Horning ◽  
...  
Keyword(s):  
High Resolution ◽  
Mass Spectrometer ◽  
Protein Complex ◽  
Protein Complexes ◽  
Mass Range ◽  
Ion Source ◽  
High Mass ◽  
Ligand Complex ◽  
Surface Induced Dissociation ◽  
Orbitrap Mass Spectrometer

Herein we demonstrate the first adaptation of surface-induced dissociation in a modified high-mass range, high-resolution Orbitrap mass spectrometer. The SID device was designed to be installed in the Q-Exactive series of Orbitrap mass spectrometers with minimal disruption of standard functions. The performance of the SID-Orbitrap instrument has been demonstrated with several protein complex and ligand-bound protein complex systems ranging from 53 to 336 kDa. We also address the effect of ion source temperature on native protein-ligand complex ions as assessed by SID. Results are consistent with previous findings on quadrupole time-of-flight instruments and suggest that SID coupled to high-resolution MS is well-suited to provide information on the interface interactions within protein complexes and ligand-bound protein complexes. <br>

Surface-Induced Dissociation of Noncovalent Protein Complexes in an Extended Mass Range Orbitrap Mass Spectrometer

2018 ◽  
Author(s):  
Zachary VanAernum ◽  
Joshua D. Gilbert ◽  
Mikhail E. Belov ◽  
Alexander A. Makarov ◽  
Stevan R. Horning ◽  
...  
Keyword(s):  
High Resolution ◽  
Mass Spectrometer ◽  
Protein Complex ◽  
Protein Complexes ◽  
Mass Range ◽  
Ion Source ◽  
High Mass ◽  
Ligand Complex ◽  
Surface Induced Dissociation ◽  
Orbitrap Mass Spectrometer

Herein we demonstrate the first adaptation of surface-induced dissociation in a modified high-mass range, high-resolution Orbitrap mass spectrometer. The SID device was designed to be installed in the Q-Exactive series of Orbitrap mass spectrometers with minimal disruption of standard functions. The performance of the SID-Orbitrap instrument has been demonstrated with several protein complex and ligand-bound protein complex systems ranging from 53 to 336 kDa. We also address the effect of ion source temperature on native protein-ligand complex ions as assessed by SID. Results are consistent with previous findings on quadrupole time-of-flight instruments and suggest that SID coupled to high-resolution MS is well-suited to provide information on the interface interactions within protein complexes and ligand-bound protein complexes. <br>

scholarly journals Surface-Induced Dissociation of Noncovalent Protein Complexes in an Extended Mass Range Orbitrap Mass Spectrometer

2019 ◽  
Vol 91 (5) ◽  
pp. 3611-3618 ◽  
Author(s):  
Zachary L. VanAernum ◽  
Joshua D. Gilbert ◽  
Mikhail E. Belov ◽  
Alexander A. Makarov ◽  
Stevan R. Horning ◽  
...  
Keyword(s):  
Mass Spectrometer ◽  
Protein Complexes ◽  
Mass Range ◽  
Surface Induced Dissociation ◽  
Orbitrap Mass Spectrometer ◽  
Noncovalent Protein

Use of benchtop exactive high resolution and high mass accuracy orbitrap mass spectrometer for screening in horse doping control

2011 ◽  
Vol 700 (1-2) ◽  
pp. 126-136 ◽  
Author(s):  
Yves Moulard ◽  
Ludovic Bailly-Chouriberry ◽  
Sophie Boyer ◽  
Patrice Garcia ◽  
Marie-Agnès Popot ◽  
...  
Keyword(s):  
High Resolution ◽  
Mass Spectrometer ◽  
Mass Accuracy ◽  
Doping Control ◽  
High Mass ◽  
High Mass Accuracy ◽  
Orbitrap Mass Spectrometer

scholarly journals Localization of Protein Complex Bound Ligands by Surface-Induced Dissociation High-Resolution Mass Spectrometry

2018 ◽  
Vol 90 (21) ◽  
pp. 12796-12801 ◽  
Author(s):  
Florian Busch ◽  
Zachary L. VanAernum ◽  
Yue Ju ◽  
Jing Yan ◽  
Joshua D. Gilbert ◽  
...  
Keyword(s):  
Mass Spectrometry ◽  
High Resolution ◽  
Protein Complex ◽  
High Resolution Mass Spectrometry ◽  
Surface Induced Dissociation ◽  
High Resolution Mass ◽  
Resolution Mass

scholarly journals High-resolution extracted ion chromatography, a new tool for metabolomics and lipidomics using a second-generation orbitrap mass spectrometer

2009 ◽  
Vol 23 (10) ◽  
pp. 1411-1418 ◽  
Author(s):  
Albert Koulman ◽  
Gary Woffendin ◽  
Vinod K. Narayana ◽  
Helen Welchman ◽  
Catharina Crone ◽  
...  
Keyword(s):  
High Resolution ◽  
Mass Spectrometer ◽  
Ion Chromatography ◽  
Second Generation ◽  
Orbitrap Mass Spectrometer

scholarly journals Prediction of Drug-Target Binding Kinetics for Flexible Proteins by Comparative Binding Energy Analysis

2021 ◽  
Author(s):  
Ariane Nunes Alves ◽  
Fabian Ormersbach ◽  
Rebecca Wade
Keyword(s):  
Binding Energy ◽  
Crystal Structures ◽  
Protein Complex ◽  
Protein Complexes ◽  
Combine Analysis ◽  
Least Squares Regression ◽  
Ligand Complex ◽  
Kinetic Rates ◽  
Multiple Structures ◽  
Comparative Binding

<div>There is growing consensus that the optimization of the kinetic parameters for drug-protein binding leads to improved drug efficacy. Therefore, computational methods have been developed to predict kinetic rates and to derive quantitative structure-kinetic relationships (QSKRs). Many of these methods are based on crystal structures of ligand-protein complexes. However, a drawback is that each protein-ligand complex is usually treated as having a single structure. Here, we present a modification of COMparative BINding Energy (COMBINE) analysis, which uses the structures of protein-</div><div>ligand complexes to predict binding parameters. We introduce the option to use multiple structures to describe each ligand-protein complex into COMBINE analysis and</div><div>apply this to study the effects of protein flexibility on the derivation of dissociation rate constants (k<sub>off</sub>) for inhibitors of p38 mitogen-activated protein (MAP) kinase, which has a flexible binding site. Multiple structures were obtained for each ligand-protein complex by performing docking to an ensemble of protein configurations obtained from molecular dynamics simulations. Coefficients to scale ligand-protein interaction energies determined from energy-minimized structures of ligand-protein complexes were obtained by partial least squares regression and allowed the computation of k<sub>off</sub> values. The QSKR model obtained using single, energy minimized crystal structures for each ligand-protein complex had a higher predictive power than the QSKR model obtained with multiple structures from ensemble docking. However, the incorporation of protein-ligand flexibility helped to highlight additional ligand-protein interactions that lead to longer residence times, like interactions with residues Arg67 and Asp168, which are close to the ligand in many crystal structures, showing that COMBINE analysis is a promising method to design leads with improved kinetic rates for flexible proteins.</div>

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