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

doi:10.1007/s40242-025-5154-1

Chemical Research in Chinese Universities ›› 2026, Vol. 42 ›› Issue (2): 586-593.doi: 10.1007/s40242-025-5154-1

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

DU Zhuoyuan^1,2, LUAN Moujun³, HOU Zhuanghao^1,2,4, HUANG Guangming^1,2,5

1. The First Affiliated Hospital of USTC, University of Science and Technology of China, Hefei 230001, P. R. China;
2. School of Chemistry and Materials Science, University of Science and Technology of China, Hefei 230026, P. R. China;
3. Experimental Center of Clinical Research, the First Affiliated Hospital of Anhui University of Chinese Medicine, Hefei 230001, P. R. China;
4. Hefei National Research Center for Physical Sciences at the Microscale, University of Science and Technology of China, Hefei 230001, P. R. China;
5. National Synchrotron Radiation Laboratory, University of Science and Technology of China, Hefei 230029, P. R. China

Received:2025-07-22 Online:2026-04-01 Published:2026-04-02
Contact: HOU Zhuanghao,E-mail:zhuanhao@ustc.edu.cn;HUANG Guangming,E-mail:gmhuang@ustc.edu.cn E-mail:zhuanhao@ustc.edu.cn;gmhuang@ustc.edu.cn
Supported by:
This work was supported by the Strategic Priority Research Program of the Chinese Academy of Sciences (No. XDB0450201), the National Natural Science Funds for Distinguished Young Scholar, China (No. 22025405), the Fundamental Research Funds for the Central Universities, China (Nos. WK2060190104, WK9990000136), and the USTC Research Funds of the Double First-Class Initiative, China (No. YD2060006007).

Abstract

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 concentration-mediated conformational modulation of the protein.

Key words: Electrospray ionization, Dimethyl sulfoxide (DMSO), Molecular dynamics, Protein structure

DU Zhuoyuan, LUAN Moujun, HOU Zhuanghao, HUANG Guangming. Effect of Dimethyl Sulfoxide on Lysozyme Structural Stability During Electrospray Ionization Revealed by Molecular Dynamics Simulations[J]. Chemical Research in Chinese Universities, 2026, 42(2): 586-593.

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

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