1st International and 10th National Iranian Conference on Bioinformatics

Home Accepted Papers

Identification of effective natural compounds for reducing α-Synuclein aggregation involved in Parkinson's disease using Molecular docking on the ZINC database

Paper ID : 1334-ICB10

Authors:

میلاد لگزیان *, مرضیه گلستان فرد, ملیحه محمدی, آرزو قهقایی

گروه زیست شناسی،دانشکده علوم،دانشگاه سیستان وبلوچستان،زاهدان،ایران

Abstract:

Parkinson's disease is one of the most common neurodegenerative disorders in the elderly age. One of the mechanisms involved in neurodegeneration is related to the aggregation of the presynaptic protein α-synuclein. Despite numerous studies and efforts, discovering compounds that can serve as promising inhibitors and delay α-synuclein aggregation remains an important challenge. This study aims to identify potential compounds that inhibit α-synuclein accumulation using structure-based virtual screening in ZINC's natural compounds Database. Initially, the structure of human α-synuclein covering the full sequence of the protein (PDB ID:1XQ8) was retrieved and prepared from the Protein Data Bank. The natural compound library from the ZINC database that contains more than 340,000 compounds was prepared. The potential α-synuclein binding pocket contained was identified by the literature review. It contained four key residues, including L38, V40, K43, and K45, used to create docking constrain. Molecular docking studies at three different precision levels, including HTVS (High throughput virtual screening), SP (standard precision), and XP (extra precision), were performed by Schrodinger 2021-2. Subsequently, the MM-GBSA method estimated the binding free energy between top-ranked ligands and the protein. The analysis of the molecular docking calculation showed that the compounds ZINC31169817 ()1S(-1,5-Anhydro-1-)2,6-dihydroxy-4-methylphenyl(-D-glucitol), ZINC12405202()1R,2S,3R,4S,5R,6S(-6-Methoxy-1,2,3,4,5-cyclohexanepentol), Compound825 (}3-)Hexopyranosyloxy(-2-[(27)-2-penten-1-yl]cyclopentyl}acetic acid) with docking score -7.998, -7.711, -7.225 Kcal/mol and the binding free energy -29.69, -26.57, -28.56 have the highest affinity for interaction to α-synuclein monomer. The identified candidates need to verify by molecular dynamics simulation before any in-invitro study.

Keywords:

Parkinson's disease, α-synuclein, aggregation, Molecular docking, ZINC Natural Library

Status : Paper Accepted (Poster Presentation)