Molecular modeling and evaluation of binding mode and affinity of artemisinin-quinine hybrid and its congeners with Fe-protoporphyrin-IX as a putative receptor.

Bioinformation
Rajani Kanta MahapatraPradeep K Naik

Abstract

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 intraparasitic 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 (ΔG) 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.

Citations

Aug 31, 2017·Pharmaceutical Development and Technology·Ali RamazaniHamidreza Kheiri Manjili

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Methods Mentioned

BETA
X-ray
two hybrids

Software Mentioned

LigPrep
PPrep
Molecular Mechanics Force Fields ( OPLS -
AA
Schrodinger Glide
ISIS Draw
Schrodinger
ACDLABS
ChemSketch
OPLS

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