Computational Design of Apolipoprotein E4 Inhibitors for Alzheimer’s Disease Therapy from Traditional Chinese Medicine
Joint Authors
Chen, Calvin Yu-Chian
Lee, Cheng-Chun
Chen, Calvin Yu-Chian
Huang, Hung-Jin
Source
Issue
Vol. 2014, Issue 2014 (31 Dec. 2014), pp.1-13, 13 p.
Publisher
Hindawi Publishing Corporation
Publication Date
2014-05-21
Country of Publication
Egypt
No. of Pages
13
Main Subjects
Abstract EN
Apolipoprotein E4 (Apo E4) is the major genetic risk factor in the causation of Alzheimer’s disease (AD).
In this study we utilize virtual screening of the world’s largest traditional Chinese medicine (TCM) database and investigate potential compounds for the inhibition of ApoE4.
We present the top three TCM candidates: Solapalmitine, Isodesacetyluvaricin, and Budmunchiamine L5 for further investigation.
Dynamics analysis and molecular dynamics (MD) simulation were used to simulate protein-ligand complexes for observing the interactions and protein variations.
Budmunchiamine L5 did not have the highest score from virtual screening; however, the dynamics pose is similar to the initial docking pose after MD simulation.
Trajectory analysis reveals that Budmunchiamine L5 was stable over all simulation times.
The migration distance of Budmunchiamine L5 illustrates that docked ligands are not variable from the initial docked site.
Interestingly, Arg158 was observed to form H-bonds with Budmunchiamine L5 in the docking pose and MD snapshot, which indicates that the TCM compounds could stably bind to ApoE4.
Our results show that Budmunchiamine L5 has good absorption, blood brain barrier (BBB) penetration, and less toxicity according to absorption, distribution, metabolism, excretion, and toxicity (ADMET) prediction and could, therefore, be safely used for developing novel ApoE4 inhibitors.
American Psychological Association (APA)
Huang, Hung-Jin& Chen, Calvin Yu-Chian& Lee, Cheng-Chun& Chen, Calvin Yu-Chian. 2014. Computational Design of Apolipoprotein E4 Inhibitors for Alzheimer’s Disease Therapy from Traditional Chinese Medicine. BioMed Research International،Vol. 2014, no. 2014, pp.1-13.
https://search.emarefa.net/detail/BIM-472725
Modern Language Association (MLA)
Huang, Hung-Jin…[et al.]. Computational Design of Apolipoprotein E4 Inhibitors for Alzheimer’s Disease Therapy from Traditional Chinese Medicine. BioMed Research International No. 2014 (2014), pp.1-13.
https://search.emarefa.net/detail/BIM-472725
American Medical Association (AMA)
Huang, Hung-Jin& Chen, Calvin Yu-Chian& Lee, Cheng-Chun& Chen, Calvin Yu-Chian. Computational Design of Apolipoprotein E4 Inhibitors for Alzheimer’s Disease Therapy from Traditional Chinese Medicine. BioMed Research International. 2014. Vol. 2014, no. 2014, pp.1-13.
https://search.emarefa.net/detail/BIM-472725
Data Type
Journal Articles
Language
English
Notes
Includes bibliographical references
Record ID
BIM-472725