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

Hakan Alıcı

doi:10.18016/ksutarimdoga.vi.737200

EN TR

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

Abstract

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, inter-sheet 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.

Keywords

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

Öz

Bu araştırmada, Parkinson hastalığı ile ilişkilendirilen apha-synuclein (AS)’ in PreNAC(46-56) fibril bölütü Moleküler Dinamik Simülasyon yöntemi kullanılarak incelenmiştir. Çalışmadaki, ilk amaç PreNAC üzerine gelecekte yapılması muhtemel çalışmalar için en uygun kuvvet alanının belirlenmesidir. Literatürde biyomoleküllerin simülasyonlarında sıklıkla kullanılan yedi kuvvet alanı üzerinden yapılan değerlendirmede, başta CHARMM27 ve GROMOS53A6 olmak üzere AMBER99SB ve AMBER99SB-ILDN kuvvet alanlarının ileriki çalışmalarda ele alınmasının uygun olacağı tespit edilmiştir. Çalışmanın diğer amacı ise PreNAC arayüz için konformasyonel özelliklerin moleküler seviyede aydınlatılmasıdır. Bu kapsamda gözlemlenen önemli bulgulardan biri His50 amino asidinin en fazla konformasyonel değişim gösteren amino asit olmasıdır. Ayrıca literatürde birden fazla ailesel mutasyon içerdiği tespit edilen 53. konumdaki Thr amino asidinin yüksek konformasyonel kararlılığa sahip olduğu gözlemlenmiştir. Bunlara ilaveten, ele alınan PreNAC arayüz için tabakalar arası elektrostatik etkileşimlerin ara yüzün kararlılığı için başlıca etkileşim tipleri olduğu tespit edilmiştir. Sonuç olarak, elde edilen bulguların AS’ nin PreNAC ve benzeri fibril bölütlerinin gelecek çalışmalarına ışık tutması beklenilmektedir.

Anahtar Kelimeler

Supporting Institution

zonguldak bülent ecevit üniversitesi

Project Number

2015-22794455-03 nolu Altyapı Projesi

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Details

Primary Language

Turkish

Subjects

-

Journal Section

Research Article

Authors

Hakan Alıcı ^*
0000-0001-5105-8331
Türkiye

Publication Date

February 28, 2021

Submission Date

May 14, 2020

Acceptance Date

July 3, 2020

Published in Issue

Year 2021 Volume: 24 Number: 1

DOI

https://doi.org/10.18016/ksutarimdoga.vi.737200

IZ

https://izlik.org/JA27GZ96XL

Cite

RIS / Bibtex

APA

Alıcı, H. (2021). Alpha-synuclein’ in PreNAC(46-56) Fibril Bölütünün Moleküler Dinamik Simülasyon Yöntemi ile Konformasyonel Değerlendirmesi. Kahramanmaraş Sütçü İmam Üniversitesi Tarım Ve Doğa Dergisi, 24(1), 11-21. https://doi.org/10.18016/ksutarimdoga.vi.737200

Cited By

Parkinson Hastalığı ile İlişkilendirilen PreNAC Fibril Kesiti ve Onun A53C, A53E, A53G, A53T, A53V Mutasyonlarının Yapısal Kararlılığın Araştırılması

Süleyman Demirel Üniversitesi Fen Edebiyat Fakültesi Fen Dergisi

https://doi.org/10.29233/sdufeffd.824140