Epitope region identification challenges of intrinsically disordered proteins in neurodegenerative diseases: Secondary structure dependence of alpha-synuclein on simulation techniques and force field parameters
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Dosyalar
Tarih
2020
Dergi Başlığı
Dergi ISSN
Cilt Başlığı
Yayıncı
Wiley
Erişim Hakkı
info:eu-repo/semantics/closedAccess
Özet
Due to fast aggregation processes of many disordered proteins in neurodegenerative diseases, it is difficult to study their epitope regions at the monomeric and oligomeric levels. Computer simulations complement experiments and have been used to identify the epitope regions of proteins. Residues that adopt beta-sheet conformation play a central role in the oligomerization and aggregation mechanisms of such proteins, including alpha-synuclein, which is at the center of Parkinson's and Alzheimer's diseases. In this study, we simulated the monomeric alpha-synuclein protein in an aqueous environment to evaluate its secondary structure properties, including beta-sheet propensity, and radius of gyration by replica exchange molecular dynamics simulations. We also obtained the molecular dynamics simulation trajectories of alpha-synuclein that were conducted using various force field parameters by the David E. Shaw group. Using these trajectories, we calculated the impacts of force field parameters on alpha-synuclein secondary structure properties and radius of gyration values and obtained results are compared with our data from REMD simulations. This study shows that the chosen force field parameters and computer simulation techniques effect the predicted secondary structure properties and radius of gyration values of alpha-synuclein in water. Herewith, we illustrate the challenges in epitope region identification of intrinsically disordered proteins in neurodegenerative diseases by current computer simulations.
Açıklama
Uversky, Vladimir N./0000-0002-4037-5857; Coskuner, Orkid/0000-0002-0772-9350;
WOS:000508167000001
PubMed: 31903719
WOS:000508167000001
PubMed: 31903719
Anahtar Kelimeler
Computer Simulations, Epitope Region, Force Field Parameters, Simulation Techniques, Alpha-Synuclein
Kaynak
Chemical Biology & Drug Design
WoS Q Değeri
Q3
Scopus Q Değeri
Q2
Cilt
96
Sayı
1
