In Silico Exploration of Plant Extracts as Ache Inhibitors: Insights from Molecular Dynamics and Mm/Gbsa Analysis for Alzheimer`s Drug Development

Authors : Barış Kurt, Murat Evcil, Ayşe Baran

Pages : 715-728

Doi:10.34248/bsengineering.1640219

View : 54 | Download : 63

Publication Date : 2025-05-15

Article Type : Research Paper

Abstract :Alzheimer\\\'s disease is a long-term neurological disorder that affects memory and other cognitive abilities. Physostigmine is a drug still used in treating symptoms associated with this disease, with its primary mechanism of action being AChE inhibition. AChE plays a crucial role in cholinergic neurotransmission, and its inhibition has been linked to the improvement of symptoms in Alzheimer\\\'s disease. In this study, 34 phytochemicals detected through LC-MS/MS analysis of 13 plant species were investigated as potential alternative drug candidates to physostigmine. For this purpose, docking studies followed by molecular dynamics simulations and MM/GBSA energy calculations were performed. The results revealed that 24 out of 34 phytochemicals were either very close to physostigmine (MM/GBSA binding affinity: -26.102 kcal/mol) or better AChE inhibitors. Additionally, it was determined that physostigmine increased the flexibility of the molecule when bound to the AChE enzyme, a unique result compared to our drug candidates. Our research emphasizes the potential of plant-derived compounds as AChE inhibitors and presents promising candidates for future drug development studies. Furthermore, physostigmine\\\'s property of increasing enzyme flexibility offers a new perspective in drug design and indicates that the role of this feature in therapeutic efficacy needs to be examined in more detail.
Keywords : Medicinal plants, MM/GBSA, In silico, Drug development

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