Alpha-synuclein’ in PreNAC(46-56) Fibril Bölütünün Moleküler Dinamik Simülasyon Yöntemi ile Konformasyonel Değerlendirmesi

Bu araştırmada, Parkinson hastalığı ile ilişkilendirilen aphasynuclein (AS)’ in PreNAC(46-56) fibril bölütü Moleküler DinamikSimülasyon yöntemi kullanılarak incelenmiştir. Çalışmadaki, ilkamaç PreNAC üzerine gelecekte yapılması muhtemel çalışmalar içinen uygun kuvvet alanının belirlenmesidir. Literatürdebiyomoleküllerin simülasyonlarında sıklıkla kullanılan yedi kuvvetalanı üzerinden yapılan değerlendirmede, başta CHARMM27 veGROMOS53A6 olmak üzere AMBER99SB ve AMBER99SB-ILDNkuvvet alanlarının ileriki çalışmalarda ele alınmasının uygun olacağıtespit edilmiştir. Çalışmanın diğer amacı ise PreNAC arayüz içinkonformasyonel özelliklerin moleküler seviyede aydınlatılmasıdır. Bukapsamda gözlemlenen önemli bulgulardan biri His50 amino asidininen fazla konformasyonel değişim gösteren amino asit olmasıdır.Ayrıca literatürde birden fazla ailesel mutasyon içerdiği tespit edilen53. konumdaki Thr amino asidinin yüksek konformasyonel kararlılığasahip olduğu gözlemlenmiştir. Bunlara ilaveten, ele alınan PreNACarayüz için tabakalar arası elektrostatik etkileşimlerin ara yüzünkararlılığı için başlıca etkileşim tipleri olduğu tespit edilmiştir. Sonuçolarak, elde edilen bulguların AS’ nin PreNAC ve benzeri fibrilbölütlerinin gelecek çalışmalarına ışık tutması beklenilmektedir.

A Conformational Evaluation for PreNAC(46-56) Fibril Segment of Alpha-synuclein using Molecular Dynamic Simulation Method

In this study, the PreNAC (46-56) fibril segment of Alpha-Synuclein (AS) associated with Parkinson's disease was examined using the molecular dynamic simulation method. The first goal of the study was to determine the most suitable force field for future studies on PreNAC. In this regard, we covered seven force fields that were widely used in biomolecule simulations, and it was determined that it is appropriate to treat the AMBER99SB and AMBER99SB-ILDN force fields, mainly CHARMM27 and GROMOS53A6, for future studies. Another goal of the study was to illuminate the conformational properties of the PreNAC interface at the molecular level. One of the most important discoveries observed in this context was that His50 was the most unstable amino acid. In addition, it was observed that amino acid 53, which is known to contain more than one family mutation, sustained high conformational stability. In addition, intersheet electrostatic interactions were the dominant interaction type for the stability of PreNAC interface. As a result, the findings in this study are expected to shed light on future studies of PreNAC of AS and its similar fibril segments.

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