Amylin is a 37 amino acid peptide hormone co-secreted with insulin, which participates in the glucose homeostasis. This hormone is able to aggregate in a β-sheet conformation and deposit in islet amyloids, a hallmark in type II diabetes. Since amylin is a gene encoded hormone, this peptide has variants caused by single nucleotide polymorphisms (SNPs) that can impact its functions. The effect of these variants can be evaluated by means of computational tools, such as molecular dynamics simulations. Here, we analyzed the structural effects caused by S20G and G33R point mutations, which, according to the 1,000 Genomes Project, have frequency in East Asian and Europe populations, respectively. By means of the aggrescan software and molecular dynamics, we found that both mutations have aggregation potential and cause changes in the monomeric forms when compared with wild-type amylin. The S20G mutation has been described as pathological related, and G33R mutation may have a deleterious effect. Furthermore, comparative analyses with pramlintide, an amylin drug analogue, allowed inferring the second α-helix maintenance may be related to the aggregation potential. Our data could help to better understand the mutations influence in the wild-type amylin sequence, being a starting point for the evaluation and characterization of other variations. The data presented here also propitiate new therapy opportunities, whether creating more effective drugs to diabetes or implementing a specific treatment to the patients with these mutations. Hence, these findings could improve the lifestyle to patients with type II diabetes.
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