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Information × Registration Number 0218U005257, 0116U000937 , R & D reports Title Development of the novel methods of fluorescence diagnostics of amyloid pathologies popup.stage_title Head Trusova Valeriya, Доктор фізико-математичних наук Registration Date 07-08-2018 Organization Kharkov National University named after V.N. Karazin popup.description2 The goal of the study consisted in clarifying the role of the lipid matrix in the lysozyme transition into the aggregation-competent conformation using molecular dynamics simulations. Furthermore, we aimed at uncovering the most appropriate environmental conditions for amyloid fibril detection by the novel amyloid markers. Finally, at the last step of the study testing the ability of the compounds to report phytsico-chemical properties of DNA has been performed. The objects of the study - physical processes and mechanisms of the formation of the aggregation-competent conformation of the proteins upon the interactions with lipid bilayers of different composition, as well as the influence of the physico-chemical parameters of the environment on the sensitivity of the novel amyloid reporters to the protein aggregates. Methods of investigation - molecular dynamics simulation, molecular docking, quantum-chemical calculations, absorption and fluorescence spectroscopy. Molecular dynamics simulations of the lysozyme-lipid systems revealed that formation of the protein-lipid complexes was accompanied by the increase in the radius of gyration and the backbone root-mean-square deviation, indicating partial unfolding of the polypeptide chain on the lipid matrix. The results obtained highlight the role of both the electrostatic and hydrophobic protein-lipid interactions in the lysozyme conformational transition. Next, the ability of the novel benzanthrone and squaraine dyes to detect lysozyme and insulin amyloid fibrils appeared to be the highest at pH 7.4 and ionic strength lower than 0.15 M. Furthermore, these compound were capable of detecting the pH- and salt-induced morpoholgical changes in the fibril structure. Finally, quantum-chemical calculations allowed us to establish a correlation between the sensitivity of the Thioflavin T derivatives to amyloid fibrils and the torsional angles between the donor and acceptor moieties of the molecules, which may help to develop the improved markers of fibrillar aggregates. Product Description popup.authors В. Трусова К. Вус О. Рижова popup.nrat_date 2020-04-02 Close