Effect of Dimethyl Sulfoxide on Lysozyme Structural Stability During Electrospray Ionization Revealed by Molecular Dynamics Simulations

Abstract

Dimethyl sulfoxide (DMSO), employed as a solvent in specific electrospray ionization (ESI) mass spectrometry experimental contexts for protein characterization, serves as a two-step structure modulator. The presence of DMSO at low concentrations can protect protein structure during the electrospray process, while DMSO at higher concentrations would disrupt protein structure. However, these DMSO concentration-mediated effects on protein structure remain unclear. Herein, we employed molecular dynamics (MD) simulations for probing the effect on protein structure at different DMSO concentrations. Our findings showed a transitional tend to decrease the charge states of lysozyme due to the evaporation behavior of DMSO clusters and provide direct evidence of concentration-mediated variations on secondary structure, hydrogen bonds, and salt bridges of lysozyme. These findings revealed protective effect of DMSO-protein interactions on the structure of lysozyme at low concentrations, but a destructive effect at high concentrations. Our study offers novel insights into the process that DMSO concentrationmediated conformational modulation of the protein.

Keywords

Electrospray ionization / Dimethyl sulfoxide (DMSO) / Molecular dynamics / Protein structure

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