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Inhibitory mechanism of n-MTAB AuNPs for α-synuclein aggregation

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Abstract

Objective

The aggregation of alpha-synuclein (α-syn) is closely related to the pathogenesis and dysfunction of Parkinson’s disease.

Methods

To investigate the potential of nanoparticlemediated therapy, the interactive mechanism between α-syn and n-myristyltrimethylammonium bromide (MTAB) Gold nanoparticles (AuNPs) with different diameters was explored by molecular dynamics simulations.

Results

The results indicated that there was a directional interaction between α-syn and n-MTAB AuNPs, in which the driving force for the binding of the C-terminus in α-syn came from electrostatic interactions and the nonamyloid β component (NAC) domain exhibited weak hydrophobic interactions as well as electrostatic interaction, thereby preventing α-syn aggregation. Energy statistics and analysis showed that for 5-MTAB AuNPs, acidic amino acids such as Glu and Asp played a very important role.

Conclusions

This study not only demonstrated a theoretical foundation for the behavior of biomolecules directionally adsorbed on the surface of biofunctional nanoparticles but also indicated that 5-MTAB AuNPs may be a potential inhibitor against α-syn protein aggregation.

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Acknowledgements

The technical support from GanSu Computing Center and the Supercomputing Center of Cold and Arid Region Environment and Engineering Research Institute of Chinese Academy of Sciences are acknowledged.

Funding

This work was supported by the Natural Science Foundation of Gansu Province (no. 20JR5RA271).

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Authors and Affiliations

  1. College of Chemistry and Chemical Engineering, Lanzhou University, Lanzhou, 730000, China

    Rui Rui Liu, Hong Lin Zhai, Min Zhu, Hai Ping Shao & Tian Hua Wang

  2. Key Laboratory of Comprehensive and Highly Efficient Utilization of Salt Lake Resources, Key Laboratory of Salt Lake Resources Chemistry of Qinghai Province, Qinghai Institute of Salt Lakes, Chinese Academy of Sciences, Xining, 810008, Qinghai, China

    Rui Rui Liu

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  1. Rui Rui Liu
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  2. Hong Lin Zhai
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  3. Min Zhu
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Contributions

Ruirui Liu: methodology, software, investigation, visualization, and writing—original draft. Hong Lin Zhai: conceptualization, supervision, writing—review and Editing, and funding acquisition. Min Zhu, Hai Ping Shao, and Tian Hua Wang: software and validation.

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Correspondence to Hong Lin Zhai.

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Liu, R.R., Zhai, H.L., Zhu, M. et al. Inhibitory mechanism of n-MTAB AuNPs for α-synuclein aggregation. J Mol Model 29, 103 (2023). https://doi.org/10.1007/s00894-023-05513-8

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