Investigation of macromolecules with simulation techniques

Alzheimer's Disease is a neurodegenerative disease that occurs due to the harmful effects of Aβ (Aβ40 and Aβ42) plaques in the brain. Therefore, the factors affecting the stability of the protein structure are very important, especially for the determination of therapeutic agents. In this study, the protein structure in which the Aβ40 and Aβ42 isoforms are intertwined in the ratio of 5:5 and 8:8 were investigated with molecular simulation techniques both by keeping the pressure constant (NPT-Isobaric Cluster) and without keeping the pressure constant (NVT-Canonical Cluster). As a result of the study, analyzes on whether the system is stable or not were obtained. Considering the results of the analysis, it was seen that the average Rmsd, hydrogen bond and beta contents values were effective on the stability of the system. It has been determined that the average Rmsd, hydrogen bond, beta contents and contact numbers between C's agree and the 8:8 ratio system is more stable than the 5:5 ratio system. In addition, the hydrophobic regions specified in the literature were found by measuring the Sasa values and their compatibility with the literature was shown. In addition, in this study, the salt bridges between Glu22/Asp23-Lys28 mentioned in the literature were observed and emphasized. The interactions that observed between Aβ40 and Aβ42 isoforms suggested that the two structures could fibrillate together.