Identification of new alpha-synuclein fibrillogenesis inhibitor using in silico structure-based virtual screening.
J Mol Graph Model
; 108: 108010, 2021 11.
Article
en En
| MEDLINE
| ID: mdl-34425419
ABSTRACT
Abnormal aggregation and accumulation of alpha-synuclein (αSN) in existing neurons is associated with Parkinson's disease (PD) as one of the age-related neurodegenerative disorders. Inhibition of αSN fibrillogenesis could be considered as a solution for PD diseases treatment. Here, virtual screening (VS) approach was used to investigate available ligands in PubChem library with structural similarity with Dihydromyricetin (DHM) (as a recently introduced suitable candidate for designing of novel antiPD drugs) against aggregation of αSN chains. Primary screening identified 314 promising molecules for αSN monomer, which were further analyzed in details by their binding energy and binding modes through molecular docking method. Evidently, the compound with PubChem ID of 100968625 displayed the lowest free binding energy with ΔG0 = -7.1 kcal.mol-1 and was selected for further analysis using molecular dynamics (MD) simulation method. Analysis of MD trajectories showed that molecules of the selected ligand interact with αSN trimer via H-bond interaction and destabilize the compact structure of αSN trimer. Further, prompt in vivo testing to validate the antiPD inhibition efficiency by this molecule can save lives.
Palabras clave
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Enfermedad de Parkinson
/
Alfa-Sinucleína
Tipo de estudio:
Diagnostic_studies
/
Screening_studies
Límite:
Humans
Idioma:
En
Año:
2021
Tipo del documento:
Article