Work

Computational exploration of palmitoyl-protein thioesterase 1 inhibition by Juniperus phoenicea L. for anti-dementia treatment

Year: 2024

Type: article

Abstract: Objectives: L., a plant used in traditional Chinese medicine, as a potential inhibitor of palmitoyl-protein thioesterase 1 (PPT1), an enzyme associated with dementia. Methods: docking against PPT1 (PDB ID: 1EH5). Docking simulations were performed in YASARA Structure with VINA scoring. Top-ranked ligands were subjected to ADMET analysis (admetlab 2.0, Protox 3.0) and PASS bioactivity prediction. Stability and reactivity were analyzed with DFT calculations (Gaussian 09), and 500 ns MD simulations (YASARA Structure, AMBER 14 force field) to assess protein-ligand complex stability. MM-PBSA was used to calculate binding free energies. Results: -pentoside (0.423) than amentoflavone (0.287) for dementia treatment. DFT calculations revealed similar electronic properties for both ligands, although amentoflavone showed slightly more favorable values. MD simulations demonstrated that amentoflavone, compared with to galantamine, had superior binding stability in the PPT1 binding pocket. Conclusion: phytochemicals, given that PPT1 is a target for developing new dementia medications. Our findings identified amentoflavone as a promising candidate for further investigation. These findings warrant further research to validate this compound's potential as a PPT1 inhibitor for dementia treatment.

Source: Journal of Taibah University Medical Sciences

DOI: 10.1016/j.jtumed.2024.12.005

Authors: Riyan A. Putera Irsal, Gusnia Meilin Gholam, Maheswari Alfira Dwicesaria, Tiyara F. Mansyah, Fernanda Chairunisa

Institutions: IPB University, Nasional University

Language: English

Topic: Computational Drug Discovery Methods

Subfield: Computational Theory and Mathematics

Field: Computer Science

Domain: Physical Sciences

SDG: Good health and well-being

Open Access status: gold

Estimated APC paid: $625