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

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

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.

• Jezik: Angleški jezik
• Ključne besede: fibrilization, beta-lactoglobulin, amyloids, MD
• Vrsta gradiva: Članek v reviji
• Tipologija: 1.01 - Izvirni znanstveni članek
• Organizacija: FKKT - Fakulteta za kemijo in kemijsko tehnologijo
• Status publikacije: Objavljeno
• Različica publikacije: Recenzirani rokopis
• Leto izida: 2024
• Št. strani: 13 str.
• Številčenje: Vol. , iss.
• PID: 20.500.12556/RUL-164940
• UDK: 577.322:544.77.022.524
• ISSN pri članku: 0942-9352
• DOI: 10.1515/zpch-2024-0761
• COBISS.SI-ID: 214767363
• Datum objave v RUL: 18.11.2024

Gradivo je del revije

• Naslov: Zeitschrift für physikalische Chemie
• Skrajšan naslov: Z. phys. Chem.
• Založnik: De Gruyter
• ISSN: 0942-9352
• COBISS.SI-ID: 15027205

Licence

• Licenca: CC BY-NC-ND 4.0, Creative Commons Priznanje avtorstva-Nekomercialno-Brez predelav 4.0 Mednarodna
• Povezava: http://creativecommons.org/licenses/by-nc-nd/4.0/deed.sl
• Opis: Najbolj omejujoča licenca Creative Commons. Uporabniki lahko prenesejo in delijo delo v nekomercialne namene in ga ne smejo uporabiti za nobene druge namene.

Sekundarni jezik

• Jezik: Slovenski jezik
• Ključne besede: fibrilizacija, beta-laktoglobulin, amiloid, MD

Projekti

• Financer: NIH - National Institutes of Health
• Številka projekta: RM1GM135136
• Naslov: Solvation modeling for next-gen biomolecule simulations