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A Comprehensive In Silico Method to Study the QSTR of the Aconitine Alkaloids for Designing Novel Drugs
- Source :
- Molecules, Vol 23, Iss 9, p 2385 (2018), Molecules, Molecules : A Journal of Synthetic Chemistry and Natural Product Chemistry, Volume 23, Issue 9
- Publication Year :
- 2018
- Publisher :
- MDPI AG, 2018.
-
Abstract
- A combined in silico method was developed to predict potential protein targets that are involved in cardiotoxicity induced by aconitine alkaloids and to study the quantitative structure&ndash<br />toxicity relationship (QSTR) of these compounds. For the prediction research, a Protein-Protein Interaction (PPI) network was built from the extraction of useful information about protein interactions connected with aconitine cardiotoxicity, based on nearly a decade of literature and the STRING database. The software Cytoscape and the PharmMapper server were utilized to screen for essential proteins in the constructed network. The Calcium-Calmodulin-Dependent Protein Kinase II alpha (CAMK2A) and gamma (CAMK2G) were identified as potential targets. To obtain a deeper insight on the relationship between the toxicity and the structure of aconitine alkaloids, the present study utilized QSAR models built in Sybyl software that possess internal robustness and external high predictions. The molecular dynamics simulation carried out here have demonstrated that aconitine alkaloids possess binding stability for the receptor CAMK2G. In conclusion, this comprehensive method will serve as a tool for following a structural modification of the aconitine alkaloids and lead to a better insight into the cardiotoxicity induced by the compounds that have similar structures to its derivatives.
- Subjects :
- 0301 basic medicine
Quantitative structure–activity relationship
In silico
Quantitative Structure-Activity Relationship
Pharmaceutical Science
Computational biology
Molecular Dynamics Simulation
alkaloids
Article
Analytical Chemistry
Protein–protein interaction
lcsh:QD241-441
03 medical and health sciences
chemistry.chemical_compound
lcsh:Organic chemistry
Protein Interaction Mapping
Drug Discovery
Aconitine
heterocyclic compounds
quantitative structure–toxicity relationship (QSTR)
Protein Interaction Maps
Physical and Theoretical Chemistry
String database
Cardiotoxicity
Organic Chemistry
Reproducibility of Results
Protein kinase II
Molecular Docking Simulation
030104 developmental biology
chemistry
Chemistry (miscellaneous)
Docking (molecular)
Drug Design
docking
network
aconitine
Molecular Medicine
Subjects
Details
- ISSN :
- 14203049
- Volume :
- 23
- Database :
- OpenAIRE
- Journal :
- Molecules
- Accession number :
- edsair.doi.dedup.....b5d33665f04cee31b661bc9a9a77e4f6