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Abstract
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Article Information:
Molecular Modeling Evaluation of the Antimalarial Activity of Artemisinin Analogues: Molecular Docking and Rescoring using Prime/MM-GBSA Approach
Mani Srivastava, Harvinder Singh and Pradeep Kumar Naik
Corresponding Author: Pradeep Kumar Naik
Submitted: 2009 July, 11
Accepted: 2009 July,24
Published: 2010 March, 10 |
Abstract:
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Artemisinin, a class of sesquiterpene endoperoxide, has been the objective of numerous studies to
prepare better and safer anti-malarial drugs. A library of artemisinin analogues has been designed consisting
of 144 analogues. The combined approaches of docking-molecular mechanics based on generalized
Born/surface area (MM-GBSA) solvation model showed that artemisinin and its structural derivatives approach
haem by pointing O1 and O2 at the endoperoxide linkage toward the iron center, a mechanism that is controlled
by steric hindrance. A linear correlation was observed between the O-Fe distance and Glide score and binding
free energy w ith correlation coefficient (R2) of 0.658 and 0.707. Quantitative structure activity relationships
were developed between the anti-malarial activity (pIC50) of these compounds and molecular descriptors like
docking score and binding free energy. Using Glide score and binding free energy the R2 were found in the
range of 0.763 to 0.734 and 0.718 to 0.786 indicating that the predictive capabilities of the models were
acceptable. Low level of root means square error for the majority of inhibitors which establish the docking and
prime/MM-GBSA based prediction model as an efficient tool for generating more potent and specific inhibitors
of haem by testing rationally designed lead compounds based on artemisinin derivatives.
Key words: Artemisinin, molecular docking, prime/MM-GBSA, virtual screening, , ,
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Cite this Reference:
Mani Srivastava, Harvinder Singh and Pradeep Kumar Naik, . Molecular Modeling Evaluation of the Antimalarial Activity of Artemisinin Analogues: Molecular Docking and Rescoring using Prime/MM-GBSA Approach. , (2): Page No: 83-102.
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ISSN (Online): 2041-0778
ISSN (Print): 2041-076X |
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