MOLECULAR DOCKING AND MOLECULAR DYNAMICS STUDIES OF ACALYPHA INDICA L. PHYTOCHEMICAL CONSTITUENTS WITH CASPASE-3

ELLIN FEBRINA; RYAN KHUNAM ALAMHARI; AIYI ASNAWI; RIZKY ABDULAH; KERI LESTARI; JUTTI LEVITA; UNANG SUPRATMAN

doi:10.22159/ijap.2021.v13s4.43861

Authors

ELLIN FEBRINA Department of Chemistry, Faculty of Mathematics and Natural Sciences, Department of Pharmacology and Clinical Pharmacy, Faculty of Pharmacy, Universitas Padjadjaran, Jl. Raya Bandung-Sumedang km. 21, Jatinangor, 45363, Indonesia
RYAN KHUNAM ALAMHARI Department of Pharmacochemistry, Faculty of Pharmacy, Universitas Bhakti Kencana, Jl. Soekarno-Hatta No. 754, Bandung, 40617, Indonesia
AIYI ASNAWI Department of Pharmacochemistry, Faculty of Pharmacy, Universitas Bhakti Kencana, Jl. Soekarno-Hatta No. 754, Bandung, 40617, Indonesia
RIZKY ABDULAH Department of Pharmacology and Clinical Pharmacy, Faculty of Pharmacy, Universitas Padjadjaran, Jl. Raya Bandung-Sumedang km. 21, Jatinangor, 45363, Indonesia
KERI LESTARI Department of Pharmacology and Clinical Pharmacy, Faculty of Pharmacy, Universitas Padjadjaran, Jl. Raya Bandung-Sumedang km. 21, Jatinangor, 45363, Indonesia, Center of Excelence in Higher Education for Pharmaceutical Care Innovation, Universitas Padjadjaran, Jl. Dipatiukur No. 35, Bandung, 40132, Indonesia
JUTTI LEVITA Department of Pharmacology and Clinical Pharmacy, Faculty of Pharmacy, Universitas Padjadjaran, Jl. Raya Bandung-Sumedang km. 21, Jatinangor, 45363, Indonesia
UNANG SUPRATMAN Department of Chemistry, Faculty of Mathematics and Natural Sciences, Central Laboratory, Universitas Padjadjaran, Jl. Raya Bandung-Sumedang km. 21, Jatinangor, 45363, Indonesia

DOI:

https://doi.org/10.22159/ijap.2021.v13s4.43861

Keywords:

Acalypha indica L., Apoptosis, Caspase-3, Molecular docking, Molecular dynamics

Abstract

Objective: This study investigated the structure-based molecular interactions between phytochemical constituents of Acalypha indica L. and caspase-3.

Methods: Thirty-three phytochemical constituents of A. indica were screened against caspase-3. The X-ray crystal structure of human caspase-3 was retrieved from https://www.rcsb.org/structure/. The molecular interactions of the phytochemicals were studied using the AutoDock 4.2 software and followed by molecular dynamics (MD) simulations using the Amber18 software.

Results: From this study, 25 screened phytochemicals were found to have a better binding mode than the native ligand. Moreover, the binding stability of the top four hits evaluated by MD indicated that the hydrogen bonds in MD were quite different from the molecular docking results due to the massive receptor and ligand movement in the MD simulations. However, with the exception of stigmasterol, all ligands were able to stabilize the protein.

Conclusion: This study suggested that γ-sitosterol acetate, β-sitosterol acetate, and γ-sitosterol might be able to induce caspase-3, thereby activating apoptosis. These high-affinity compounds can bind to caspase-3 more efficiently and were able to stabilize the protein. Therefore, they have the potential to be used as lead compounds in the treatment of cancer.

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