title: Molecular modeling and evaluation of binding mode and affinity of artemisinin-quinine hybrid and its congeners with Fe-protoporphyrin-IX as a putative receptor.
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.
authors.affiliation: School of Life Sciences, Sambalpur University, Burla, Odisha-768019, India; School of Biotechnology, KIIT University, Bhubaneswar, Odisha-751024, India. rmohapatra@kiitbiotech.ac.in
authors.forename: Rajani Kanta
authors.initials: RK
authors.lastname: Mahapatra
authors.forename: Niranjan
authors.initials: N
authors.lastname: Behera
authors.forename: Pradeep Kumar
authors.initials: PK
authors.lastname: Naik