The mechanism of self-association of human ▫$\gamma$▫-D crystallin from molecular dynamics simulations

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

The aggregation of human $\gamma$-D crystallin is associated with the age-onset cataract formation. Here, we extensively investigated the self-association mechanism of human $\gamma$-D crystallin through molecular dynamics computer simulations. By mutating the protein surface we found that electrostatic interactions between charged amino acids play a crucial role in its self-association. We have confirmed the two-fold role of arginine molecules. If they are located as residues on the protein surface they can initiate protein contacts and contribute to their stickiness with noteworthy hydrophobic interactions through stacking of their methylene groups. But if they are added as free arginine in the protein solution they can also stabilize it, by associating with the protein surface and also with themselves to form effective inter-protein spacers that obstruct protein aggregation.

• Language: English
• Keywords: γ-D crystallin, self-assembly, arginine, MD simulation
• Work type: Article
• Typology: 1.01 - Original Scientific Article
• Organization: FKKT - Faculty of Chemistry and Chemical Technology
• Publication status: Published
• Publication version: Version of Record
• Year: 2023
• Number of pages: 8 str.
• Numbering: Vol. 386, art. 122461
• PID: 20.500.12556/RUL-148272
• UDC: 577.322
• ISSN on article: 0167-7322
• DOI: 10.1016/j.molliq.2023.122461
• COBISS.SI-ID: 157958915
• Publication date in RUL: 09.08.2023

Record is a part of a journal

• Title: Journal of molecular liquids
• Shortened title: J. mol. liq.
• Publisher: Elsevier
• ISSN: 0167-7322
• COBISS.SI-ID: 15382277

Licences

• License: CC BY-NC 4.0, Creative Commons Attribution-NonCommercial 4.0 International
• Link: http://creativecommons.org/licenses/by-nc/4.0/
• Description: A creative commons license that bans commercial use, but the users don’t have to license their derivative works on the same terms.

Secondary language

• Language: Slovenian
• Keywords: gama-D-kristalin, samozdruževanje, arginin, simulacija molekulske dinamike

Projects

• Funder: NIH - National Institutes of Health
• Project number: RM1GM135136

• Funder: ARRS - Slovenian Research Agency
• Project number: BI-US/22-24-125