The influence of glycine on ▫$\beta$▫-lactoglobulin amyloid fibril formation – computer simulation study

Jaklin, Matej (author), Brudar, Sandi (author), Hribar-Lee, Barbara (author)

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.

• Language: English
• Keywords: fibrilization, beta-lactoglobulin, amyloids, MD
• Work type: Article
• Typology: 1.01 - Original Scientific Article
• Organization: FKKT - Faculty of Chemistry and Chemical Technology
• Publication status: Published
• Publication version: Author Accepted Manuscript
• Year: 2024
• Number of pages: 13 str.
• Numbering: Vol. , iss.
• PID: 20.500.12556/RUL-164940
• UDC: 577.322:544.77.022.524
• ISSN on article: 0942-9352
• DOI: 10.1515/zpch-2024-0761
• COBISS.SI-ID: 214767363
• Publication date in RUL: 18.11.2024

Record is a part of a journal

• Title: Zeitschrift für physikalische Chemie
• Shortened title: Z. phys. Chem.
• Publisher: De Gruyter
• ISSN: 0942-9352
• COBISS.SI-ID: 15027205

Licences

• License: CC BY-NC-ND 4.0, Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International
• Link: http://creativecommons.org/licenses/by-nc-nd/4.0/
• Description: The most restrictive Creative Commons license. This only allows people to download and share the work for no commercial gain and for no other purposes.

Secondary language

• Language: Slovenian
• Keywords: fibrilizacija, beta-laktoglobulin, amiloid, MD

Projects

• Funder: NIH - National Institutes of Health
• Project number: RM1GM135136
• Name: Solvation modeling for next-gen biomolecule simulations