HOME   |    PDF   |   


Molecular docking analysis of α-Synuclein aggregation with Anle138b



Annu Grewal, Deepak Sheokand, Vandana Saini & Ajit Kumar*



Toxicology and Computational Biology Group, Centre for Bioinformatics, Maharshi Dayanand University, Rohtak, Haryana, India; *Corresponding author



Annu Grewal - E-mail: annu.rs.bioinfo@mdurohtak.ac.in & agrewal113@gmail.com

Deepak Sheokand - E-mail: deepak.rs.bioinfo@mdurohtak.ac.in & dpk.sheo@gmail.com

Vandana Saini - E-mail: vandana.rs.bioinfo@mdurohtak.ac.in & vandanas64@gmail.com

Ajit Kumar - E-mail: akumar.cbt.mdu@gmail.com & ajitkumar.cbinfo@mdurohtak.ac.in


Article Type

Research Article



Received March 1, 2024; Revised March 31, 2024; Accepted March 31, 2024, Published March 31, 2024



α-Synuclein aggregation into toxic oligomeric species is central to Parkinsonís disease pathogenesis. Anle138b is a recently identified inhibitor of α-synuclein oligomerization showing promise in preclinical studies. This study employed computational approaches to elucidate Anle138bís mechanism of oligomer-specific action. The inhibitory potential of Anle138b against α-synuclein oligomers was evaluated by performing molecular docking studies using AutoDock Tools, followed by their binding pocket analysis. Further, protein-protein docking studies were performed using Hex8.0 to validate the aggregation inhibitory potential of Anle138b. Molecular docking revealed increasing binding affinity of Anle138b against higher order α-synuclein oligomers (dimer to decamer). Anle138b occupied oligomeric cavity and interacted with residues Thr54, Gly73, Val74 and Thr75 across several oligomers. Protein-protein docking showed that Anle138b interferes with α-synuclein decamer formation. These results highlight the oligomer-directed inhibitory mechanism of Anle138b, without hindering the monomeric forms and provide molecular insights to advance its therapeutic development for Parkinsonís and related synucleinopathies.



Molecular docking, protein-protein docking, Parkinsonís disease, α-synuclein aggregation



Grewal et al. Bioinformation 20(3): 208-222 (2024)


Edited by

Peter N Pushparaj






Biomedical Informatics



This is an Open Access article which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. This is distributed under the terms of the Creative Commons Attribution License.