Computational study of peptide interaction with mutant γ-crystallin with the aim of preventing dimerization

As we know, cataract disease is caused by the aggregation of crystallin proteins, such as alpha, beta, and gamma-crystallin, in the lens of the eye. Naturally, when mutations occur in gamma-crystallin proteins, its binding affinity to the alpha-crystallin is increased, the protein with known chaperone role. Mutant gamma-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 gamma-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 gamma-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 gamma-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.