DOI: 10.17586/2226-1494-2017-17-6-1033-1044


COMPUTER SIMULATION OF INTERACTION OF LYSINE DENDRIMERS WITH STACK OF AMYLOID PEPTIDES

E. V. Popova, D. N. Khamidova , I. M. Neelov, F. S. Komilov , F. Leermakers


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For citation: Popova E.V., Khamidova D.N., Neelov I.M., Komilov F.S., Leermakers F. Computer simulation of interaction of lysine dendrimers with stack of amyloid peptides. Scientific and Technical Journal of Information Technologies, Mechanics and Optics, 2017, vol. 17, no. 6, pp. 1033–1044 (in Russian). doi: 10.17586/2226-1494-2017-17-6-1033-1044

Abstract
Subject of Research. Dendrimers are polymer molecules that regularly branch from a single center. Dendrimers can be used as antibacterial, antiviral and anti-amyloid agents. Recently, it has been shown experimentally that some dendrimers can prevent the formation of amyloid fibrils and destroy already existing fibrils consisting of stacks of amyloid peptides. Two systems containing lysine dendrimers of the second or third generation and a stack of 16 amyloid peptides in aqueous solution were studied in the present paper. Method. The study was carried out by computer simulation with the use of the molecular dynamics method. Main Results. It was shown that lysine dendrimers of the second or third generations destroy amyloid stack and form stable complex with peptides. Both kinetics of the amyloid stack destruction and formation of complexes with dendrimers, and the equilibrium structures of the complexes formed were studied. In particular, it was shown that electrostatic interactions between charged groups of dendrimers and peptides play the main role in the destruction of stacks. In the complexes obtained, the peptides are located mainly on the surface of the dendrimer and only slightly penetrate into the complex. Practical Relevance. The data obtained can be used in the future in the treatment of Alzheimer's disease, since it is believed that one of the reasons for its occurrence is the formation of oligomers and fibrils consisting of stacks of amyloid peptides.

Keywords: lysine dendrimers, amiloid fibrils, computer simulation, molecular dynamics method

Acknowledgements. This work was supported by grants of the Russian Federation Government 074-U01 and RFBR 16-03-00775. The authors express their gratitude to Supercomputer Center of Lomonosov Moscow State University for submission of computer re-sources.

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