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Investigation of the Structural Stability of PreNAC and its A53C, A53E, A53G, A53T, A53V Mutant Fibril Segments Associated with Parkinson's Disease

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dc.creator ALICI, Hakan; ZONGULDAK BÜLENT ECEVİT ÜNİVERSİTESİ
dc.creator DEMİR, Kadir; ZONGULDAK BÜLENT ECEVİT ÜNİVERSİTESİ, FEN-EDEBİYAT FAKÜLTESİ, FİZİK BÖLÜMÜ
dc.date 2021-05-27T00:00:00Z
dc.date.accessioned 2022-05-10T11:00:37Z
dc.date.available 2022-05-10T11:00:37Z
dc.identifier https://dergipark.org.tr/tr/pub/sdufeffd/issue/62394/824140
dc.identifier 10.29233/sdufeffd.824140
dc.identifier.uri http://acikerisim.sdu.edu.tr/xmlui/handle/123456789/96248
dc.description A pathological hallmark of Parkinson's disease (PD) is the fibrillar structures formed by alpha-synuclein aggregates accumulated in the brain. In this study, we focused on an alpha-synuclein PreNAC fibril segment and it’s A53C, A53E, A53G, A53T and A53V mutations. The structural stability and the interactions between sheets of all fibril systems studied in this paper were examined using the Molecular Dynamic (MD) simulation method and thus the possibilities of these fibril segments to be target structures for future drug development efforts was evaluated. According to the findings obtained from our MD simulations, it was determined that the wild type (WT) fibril segment and its A53E, A53T and A53V fibril structures with hereditary mutations preserved significantly their stable conformational structure along the simulations, whereas the A53G mutation had a disruptive effect on the fibril segment.
dc.description Parkinson hastalığının (PD) başlıca patolojik işaretlerinden biri beyinde kümelenmiş alfa-sinüklein agregalarının oluşturdukları fibril yapılardır. Bu çalışmada PreNAC olarak adlandırılan bir alfa-sinüklein fibril kesiti ve onun 53. aminoasidinin A53C, A53E, A53G, A53T ve A53V mutasyon fibril yapıları üzerine odaklanılmıştır. Ele alınan tüm fibril kesiti sistemlerinin yapısal kararlılıkları ve yaprak tabakları arasındaki etkileşimler Moleküler Dinamik (MD) simülasyon yöntemi kullanılarak incelenmiştir. Böylece ilgilenilen fibril kesitlerinin gelecekteki muhtemel ilaç geliştirme çalışmaları için hedef yapı olabilme ihtimalleri değerlendirilmiştir. Çalışmada elde edilen bulgulara göre, vahşi tip fibril kesiti ve onun kalıtsal mutasyonlarını içeren A53E, A53T, A53V fibril kesitlerinin simülasyonlar boyunca önemli ölçüde konformasyonel formlarını kararlı bir şekilde koruduğu gözlemlenirken öte yandan A53G mutasyonunun fibril kesitini dağıtıcı bir etki gösterdiği tespit edilmiştir.
dc.format application/pdf
dc.language tr
dc.publisher Süleyman Demirel Üniversitesi
dc.publisher Süleyman Demirel University
dc.relation https://dergipark.org.tr/tr/download/article-file/1390602
dc.source Volume: 16, Issue: 1 66-76 en-US
dc.source 1306-7575
dc.source Süleyman Demirel Üniversitesi Fen Edebiyat Fakültesi Fen Dergisi
dc.subject PreNAC,Molecular Dynamics,Simulation,Parkinson’s disease
dc.subject PreNAC,Moleküler Dinamik,Simülasyon,Parkinson Hastalığı
dc.title Investigation of the Structural Stability of PreNAC and its A53C, A53E, A53G, A53T, A53V Mutant Fibril Segments Associated with Parkinson's Disease en-US
dc.title Parkinson Hastalığı ile İlişkilendirilen PreNAC Fibril Kesiti ve Onun A53C, A53E, A53G, A53T, A53V Mutasyonlarının Yapısal Kararlılığın Araştırılması tr-TR
dc.type info:eu-repo/semantics/article
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