Molecular Dynamics Simulation of the Complex of PDE5 and Evodiamine

Alzheimer's disease is an irreversible neurological disorder for which there are no effective small molecule therapeutics. A phosphodiesterase 5 (PDE5) inhibitor is a candidate medicine for the treatment of Alzheimer's disease. Rutaecarpine, an indole alkaloid found in , has inhibitory act...

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Bibliographic Details
Published in:Life (Basel, Switzerland) Switzerland), 2023-02, Vol.13 (2), p.578
Main Authors: Kobayashi, Ayame, Nakajima, Motokuni, Noguchi, Yoh, Morikawa, Ryota, Matsuo, Yukiko, Takasu, Masako
Format: Article
Language:English
Subjects:
Alkaloids
Alzheimer's disease
Care and treatment
Chemical properties
Communication
Comparative analysis
Energy
Enzymes
evodiamine
Health aspects
Hydrogen bonds
Hydrolases
Kinases
Medicinal plants
Memory
Methods
Molecular dynamics
molecular dynamics simulation
Molecular simulation
natural product
Nervous system diseases
Neurodegenerative diseases
Neurological diseases
Optimization
PDE5
Pharmacology, Experimental
Phosphorylation
Proteins
Simulation
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Summary:Alzheimer's disease is an irreversible neurological disorder for which there are no effective small molecule therapeutics. A phosphodiesterase 5 (PDE5) inhibitor is a candidate medicine for the treatment of Alzheimer's disease. Rutaecarpine, an indole alkaloid found in , has inhibitory activity for PDE5. contains more evodiamine than rutaecarpine. Therefore, we performed molecular dynamics simulations of the complex of PDE5 and evodiamine. The results showed that the PDE5 and (-)-evodiamine complexes were placed inside the reaction center compared to the case of PDE5 and (+)-evodiamine complex. The binding of (-)-evodiamine to PDE5 increased the root-mean-square deviation and radius of gyration of PDE5. In the PDE5 with (-)-evodiamine complex, the value of the root-mean-square fluctuation of the M-loop, which is thought to be important for activity, increased. This result suggests that (-)-evodiamine may have inhibitory activity.
ISSN:2075-1729
2075-1729
DOI:10.3390/life13020578