Aggregation of Amyloidogenic Peptide Uperin-Molecular Dynamics Simulations

Elena Ermakova; Olga Makshakova; Rauf Kurbanov; Ilya Ibraev; Yuriy Zuev; Igor Sedov

doi:10.3390/molecules28104070

Aggregation of Amyloidogenic Peptide Uperin-Molecular Dynamics Simulations

Molecules. 2023 May 13;28(10):4070. doi: 10.3390/molecules28104070.

Authors

Elena Ermakova¹, Olga Makshakova¹, Rauf Kurbanov¹, Ilya Ibraev², Yuriy Zuev¹, Igor Sedov^{1

2}

Affiliations

¹ Kazan Institute of Biochemistry and Biophysics, FRC Kazan Scientific Center of RAS, Lobachevsky Str., 2/31, Kazan 420111, Russia.
² Chemical Institute, Kazan Federal University, Kremlevskaya Str., 18, Kazan 420008, Russia.

Abstract

Uperin 3.5 is a remarkable natural peptide obtained from the skin of toadlets comprised of 17 amino acids which exhibits both antimicrobial and amyloidogenic properties. Molecular dynamics simulations were performed to study the β-aggregation process of uperin 3.5 as well as two of its mutants, in which the positively charged residues Arg7 and Lys8 have been replaced by alanine. All three peptides rapidly underwent spontaneous aggregation and conformational transition from random coils to beta-rich structures. The simulations reveal that the initial and essential step of the aggregation process involves peptide dimerization and the formation of small beta-sheets. A decrease in positive charge and an increase in the number of hydrophobic residues in the mutant peptides lead to an increase in the rate of their aggregation.

Keywords: aggregation; amyloid peptides; molecular dynamics simulations; uperin.

MeSH terms

Amyloid beta-Peptides / metabolism
Amyloid* / chemistry
Dimerization
Molecular Conformation
Molecular Dynamics Simulation*
Peptide Fragments / chemistry

Substances

Amyloid
Amyloid beta-Peptides
Peptide Fragments

Grants and funding

This research received no external funding.