1st International and 10th National Iranian Conference on Bioinformatics
Home Accepted Papers
Applying virtual screening approach to find out effective agonist against RXR (retinoid X receptor) as promising candidates to treat Alzheimer disease
Paper ID : 1373-ICB10
Authors:
ladan ladan mafakher *1, behzad shahbazi2, alireza rahimpour3
1مرکز تحقیقات تالاسمی و هموگلوبینوپاتی دانشگاه علوم پزشکی جندی شاپور اهواز ایران اهواز
2بخش پزشکی مولکولی انستیتو پاستور ایران ایران تهران
3دانشگاه ازاد اسلامی واحد علوم تحقیقات تهران ایران
Abstract:
Introduction:
Alzheimer's is neurodegenerative disease that causes accumulation of extensive amyloid-beta in the brain[1]. The prevalence Alzheimer of patients increased exponentially so that in United states estimates 13.7 million people will be affected by Alzheimer by 2080[2]. Alzheimer's patients can be classified into two different types including Sporadic or late-onset AD (LOAD) with prevalence of 95% and early-onset AD (EOAD) [3, 4]. In the LOAD, one of the predominate risk factor gene is APOE which dysregulation of this gene increase accumulation of amyloid-beta[5, 6]. So regulation the expression of APOE by RXR receptor as transcriptional regulator of APOE by designing Agonist against RXR receptor could be control clearance of amyloid-beta and decrease symptoms of Alzheimer[7, 8].
Material and Methods:
Two herbal Database (TCM and IBscreen) were selected as ligand libraries. Pharmit webserver was chosen to check properties of small molecules based on Lipinski's rules[9]. The selected small molecules which pass Lipinski's rules were applied to dock by SMINA package against binding site of RXR receptor[10]. The small molecules that effectively interact with RXR binding site nominated for cytotoxic and blood barrier properties analysis by OSIRIS Data Warrior[11] and BBB predictor. Small molecules that could pass blood-brain barrier and have not mutagenesis, tumorigenic, reproductive effect properties were entered in Molecular Dynamic simulation [12] and efficacy of their interaction were checked by MM/PBSA package[13, 14].
Results and Discussion:
Among total compounds of TCM and IBscreen, around thirty compounds pass Lipinski's rules and effectively interact with binding site of RXR receptor. Cytotoxic and blood brain barrier analysis revealed that all these compounds have no mutagenesis, tumorigenic, reproductive effect and able to pass blood brain barrier. Molecular dynamic simulation discovered that five compounds able to interact efficiently during simulation. MM/PBSA analysis figured out that these compounds effectively bind to binding site of RXR receptor.
Keywords:
Alzheimer disease, virtual screening, retinoid X receptor, Molecular Dynamics simulation, Molecular docking
Status : Paper Accepted (Poster Presentation)