An atomistic view to the gas phase proteome.

Area of Science:

• Biophysics
• Structural Biology
• Computational Chemistry

Background:

• Understanding protein structure in different environments is crucial for biological function.
• Electrospray ionization (ESI) is a common technique for transferring biomolecules to the gas phase for mass spectrometry.
• Previous studies have suggested significant structural changes upon gas-phase transfer.

Purpose of the Study:

• To investigate the structural integrity of proteins in the gas phase using all-atom molecular dynamics simulations.
• To create a comprehensive structural atlas of the gas-phase proteome.
• To assess the feasibility of using gas-phase structures as approximations for solution structures.

Main Methods:

• Extended all-atom molecular dynamics (MD) simulations were performed for various protein metafolds.
• Simulations covered both solution and gas phases under electrospray ionization conditions.
• Analysis focused on global and local structural features, deformability, and secondary structure preservation.

Main Results:

• Proteins unexpectedly maintain significant global and local structural features in the gas phase.
• Gas-phase structures are highly recognizable compared to solution structures, despite general compression.
• Secondary structures and deformability patterns are largely preserved during vaporization.
• Rehydration rapidly restores the solution structure from the gas-phase conformation.

Conclusions:

• Mass spectrometry techniques can provide fast approximations of protein solution structures by analyzing gas-phase conformations.
• The study challenges assumptions about extensive protein unfolding during gas-phase transfer.
• The findings have implications for structural biology and the interpretation of mass spectrometry data for proteins.