Investigation of Inhibition Effect of Nicotine and Dopamine on Alpha-synuclein
Hakan Alici
article (Uluslararası, Hakemli) | Yazar(lar): Hakan Alici | Yıl: 2021 | Dergi/Kurum: JOURNAL OF COMPUTATIONAL BIOPHYSICS AND CHEMISTRY | İndeks: WOS.SCI | DOI: 10.1142/s2737416521500265 | Anahtar Kelimeler: Parkinson's disease, alpha-synuclein, molecular dynamics, simulation, docking — Özet: Parkinson's disease (PD) is
Parkinson's disease (PD) is a progressive nervous system disorder and its pathological hallmark is the presence of fibrillar aggregates called Lewy bodies (LB) in substantia nigra. As it is also well established, alpha-synuclein is the major constituent of the LB. Although numerous experimental studies have been conducted on inhibition of alpha-synuclein aggregation, the detailed inhibitory mechanism is not still fully elucidated. In this paper, we first focused on identifying the binding modes of nicotine and dopamine to alpha-synuclein using molecular docking. Then, we performed comparative molecular dynamics (MD) simulations to enlighten the inhibition mechanism of alpha-synuclein for both dopamine and nicotine. MD simulations demonstrate that both nicotine and dopamine stabilize dominant helical structure of alpha-synuclein and so they inhibit their conformational transitions. Moreover, the favorable and unfavorable contribution residues, which play a key role in the inhibition of alpha-synuclein, were determined using MM-PBSA analysis. The findings in this study will shed light on understanding the inhibition mechanism of alpha-synuclein and guide potential drug development studies of degenerative diseases.