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The influence of glycine on β-lactoglobulin amyloid fibril formation – computer simulation study

  • Matej Jaklin ORCID logo , Sandi Brudar ORCID logo and Barbara Hribar-Lee ORCID logo EMAIL logo
Published/Copyright: November 11, 2024
Zeitschrift für Physikalische Chemie
From the journal Zeitschrift für Physikalische Chemie Volume 239 Issue 9

Abstract

Amyloids are protein aggregates involved in various protein condensation diseases. Our study aims to investigate the influence of glycine on the fibrillization mechanism of β-lactoglobulin (BLG), a model protein known to form amyloid fibrils from hydrolysed peptides in low pH aqueous solutions. We conducted atomistic molecular dynamics simulations of aqueous solutions of native and unfolded BLG in glycine buffer at pH 2.0. During the simulations we put our focus on analysing protein-protein/buffer interactions, structural electrostatic potential mapping, and the residence times of glycine and glycinium near specific amino acid residues. Glycinium cations were found to preferentially interact with specific protein residues potentially masking the outer disulfide bonds, affecting thiol deprotonation and influencing disulfide scrambling equilibrium. These interactions can potentially hinder hydrolysis and change the fibrillization pathway. Further investigations, such as constant pH MD simulations, simulations on disulfide bounded oligomers are warranted to validate these findings and deepen our understanding of protein aggregation mechanisms.

Keywords: fibrillization; beta-lactoglobulin; amyloids; MD
Corresponding author: Barbara Hribar-Lee, Faculty of Chemistry and Chemical Technology, University of Ljubljana, Večna pot, 113, SI-1000 Ljubljana, Slovenia, E-mail:

Acknowledgments

The authors acknowledge the support from the National Institutes of Health (NIH) RM1 award “Solvation modeling for next-gen biomolecule simulations” (grant No. RM1GM135136).

  1. Research ethics: Not applicable.

  2. Informed consent: Not applicable.

  3. Author contributions: All authors have accepted responsibility for the entire content of this manuscript and approved its submission.

  4. Use of Large Language Models, AI and Machine Learning Tools: None declared.

  5. Conflict of interest: The authors state no conflict of interest.

  6. Research funding: National Institutes of Health (NIH) RM1, grant No. RM1GM135136.

  7. Data availability: The datasets generated and/or analyzed during the current study are available from the corresponding author on reasonable request.

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Received: 2024-02-28
Accepted: 2024-09-10
Published Online: 2024-11-11
Published in Print: 2025-09-25

© 2024 Walter de Gruyter GmbH, Berlin/Boston

Articles in the same Issue

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  2. Preface
  3. Preface
  4. Contribution to “From Nanostructure to Function”
  5. Temporal airy pulses efficiency in thin glass dicing
  6. Surface investigations of bronze and brass statuary monuments in open-air exposure
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  9. From nanostructure to function: hierarchical functional structures in chitin and keratin
  10. The influence of glycine on β-lactoglobulin amyloid fibril formation – computer simulation study
https://doi.org/10.1515/zpch-2024-0761
Keywords for this article
fibrillization; beta-lactoglobulin; amyloids; MD

Articles in the same Issue

  1. Frontmatter
  2. Preface
  3. Preface
  4. Contribution to “From Nanostructure to Function”
  5. Temporal airy pulses efficiency in thin glass dicing
  6. Surface investigations of bronze and brass statuary monuments in open-air exposure
  7. Dual dynamic voltammetric study of the formation of ferrate ions during the electrochemical dissolution of white cast iron in the transpassive region
  8. Cetuximab-induced changes to tumor oral mucosa models probed by stimulated Raman spectromicroscopy
  9. From nanostructure to function: hierarchical functional structures in chitin and keratin
  10. The influence of glycine on β-lactoglobulin amyloid fibril formation – computer simulation study
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