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07:33
Analyzing Protein Architectures and Protein-Ligand Complexes by Integrative Structural Mass Spectrometry
Published on: October 15, 2018
Elucidating the intermolecular interactions within a desolvated protein-ligand complex. An experimental and
Elena N Kitova1, Mikyung Seo, Pierre-Nicholas Roy
1Alberta Ingenuity Centre for Carbohydrate Science and Department of Chemistry, University of Alberta, Edmonton, Alberta, Canada T6G 2G2.
Journal of the American Chemical Society
|January 4, 2008
Summary
This study details intermolecular hydrogen bonds in a protein-ligand complex using gas-phase experiments and simulations. Key interactions are identified, revealing charge-dependent structural differences and conserved H-bonds from solution to gas phase.
Area of Science:
- Biochemistry and Biophysics
- Structural Biology
- Mass Spectrometry
Background:
- Noncovalent protein-ligand complexes are crucial in biological systems.
- Understanding intermolecular interactions, particularly hydrogen bonds, is key to elucidating binding mechanisms.
- Gas-phase studies offer a unique perspective on these interactions, free from solvent effects.
Purpose of the Study:
- To characterize intermolecular hydrogen bonds within a desolvated protein-ligand complex.
- To investigate the influence of charge state on these interactions.
- To compare gas-phase interactions with crystal structures and computational predictions.
Main Methods:
- Blackbody infrared radiative dissociation-functional group replacement (BIRD/FGR) for experimental identification and quantification of H-bonds.
- Molecular dynamics (MD) simulations to model interactions at specific charge states (+8 and -8).
- Electrospray ionization (ESI) to transfer the complex from solution to the gas phase.
Main Results:
- Three specific intermolecular hydrogen bond donor-acceptor pairs were identified and quantified in the gaseous complex.
- At least two specific H-bonds appear conserved between the solution and gas phases.
- Significant structural differences and varied interaction strengths were observed between protonated and deprotonated ions, influenced by charge state.
Conclusions:
- Intermolecular hydrogen bonds play a critical role in stabilizing desolvated protein-ligand complexes.
- Gas-phase experimental and computational methods provide complementary insights into complex structure and interactions.
- Charge state significantly impacts the structural integrity and intermolecular interactions within the complex.
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