Title

Authors

Affiliation

¹School of Life Sciences, Sambalpur University, Burla, Odisha-768019, India; ²School of Biotechnology, KIIT University, Bhubaneswar, Odisha-751024, India; ³Department of Biotechnology & Bioinformatics, JUIT, Solan, Himachal Pradesh-173 215, India.

Email

rmohapatra@kiitbiotech.ac.in; *Corresponding author

Article Type

Hypothesis

Date

Received April 10, 2012; Accepted April 16, 2012; Published April 30, 2012

A recent rational approach to anti-malarial drug design is characterized as ‛‛covalent biotherapy’’ involves linking of two molecules with individual intrinsic activity into a single agent, thus packaging dual activity into a single hybrid molecule. In view of this background and reported anti malaria synergism between artemisinin and quinine; we describe the computer-assisted docking to predict molecular interaction and binding affinity of Artemisinin-Quinine hybrid and its derivatives with the intra-parasitic haeme group of human haemoglobin. Starting from a crystallographic structure of Fe-protoporphyrin-IX, binding modes, orientation of peroxide bridge [Fe-O distance], docking score and interaction energy are predicted using the docking molecular mechanics based on generalized Born/surface area [MM-GBSA] solvation model. Seven new ligands were identified with a favourable glide score [XP score] and binding free energy [∆G] with reference to the experimental structure from a data set of thirty four hybrid derivatives. The result shows the conformational property of the drug-receptor interaction and may lead to rational design and synthesis of improved potent artemisinin based hybrid antimalarial that target haemozoin formation.

Keywords

Artemisinin-Quinine Hybrid; Molecular Docking; Fe-O Distance; Binding Affinity

Citation

Mahapatra et al. Bioinformation 8(8): 369-380 (2012)
 

Edited by

P Kangueane

ISSN

0973-2063

Publisher

Biomedical Informatics

License

This is an Open Access article which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. This is distributed under the terms of the Creative Commons Attribution License.