Abstract
As we know, cataract disease is caused by the aggregation of crystallin proteins, such as α, β, and γ-crystallin, in the lens of the eye. Naturally, when mutations occur in γ-crystallin proteins, its binding affinity to the α-crystallin is increased, the protein with known chaperone role. Mutant γ-crystallin proteins also have a strong affinity to bind to each other and form large oligomers. The presence of these aggregates causes opacity of the lens of the eye and causes cataract disease. In this work, we aim to investigate whether peptides can prevent mutant γ-crystallin proteins from oligomerization/aggregation. Molecular docking and molecular dynamic simulations were used to determine how three putative amyloid-binding octapeptides (RVTWEGKF, RGTFEGRF, and RITFEIKF) bind to the mutant γ-crystallin protein. The results showed that RVTWEGKF had a more favorable binding energy for interaction with the mutant protein than RGTFEGRF and RITFEIKF. Also, in the presence of RVTWEGKF, mutant γ-crystallin is less likely to form protein dimers. Based on these findings, RGTFEGRF is proposed to be tested experimentally as a potential treatment against cataract disease.
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RM and MFR contributed in resource and funding acquisition. KJ contributed in project administration. AN contributed in project administration, resources and funding acquisition, and validation. EB conceptualized the work and completing the draft; performed data curation, analysis, validation and visualization; and wrote the original draft. All authors reviewed the final manuscript.
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Daryabari, SH., Aghamollaei, H., Jadidi, K. et al. Computational study of peptide interaction with mutant γ-crystallin with the aim of preventing dimerization. Struct Chem 34, 695–702 (2023). https://doi.org/10.1007/s11224-022-02015-w
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DOI: https://doi.org/10.1007/s11224-022-02015-w