ஜர்னல் ஆஃப் கம்ப்யூட்டர் சயின்ஸ் & சிஸ்டம்ஸ் பயாலஜி

Structural Modeling, Evolution and Ligand Interaction of KMP11 Protein of Different Leishmania Strains

Abstract

Ganesh Chandra Sahoo, Mukta Rani, Manas Ranjan Dikhit, Waquar Akhtar Ansari and Pradeep Das

The kinetoplastid-specific KMP11 protein was first described for Leishmania donovani associated with the lypophosphoglycan molecule and is localized mainly around the flagellum and flagellar pocket. This protein is well conserved among kinetoplastids and plays an analogous role in all the flagellates, irrespective of their pathogenicity in humans. The structural elucidation of this important protein may bring about information required to target KMP11 to find valid drug candidates. The atomic-resolution model of KMP11 protein of six different Leishmania strains has been determined from its amino acid sequence by using homology modeling. The stereochemical validation of modeled protein has been done by PROCHECK and Profiles-3D scores. The ligand protein interaction of the KMP11 protein models were carried out with several anti-leishmanial drugs i.e. miltefosine, sitamaquine, pentamidine, amphotericin B, SAG (sodium antimony gluconate), leishmanial peptide, paromomycin and vinblastine and an anticancer compound, sulforaphane. Glutamic acid (E) and lysine (K) of KMP11 are the key amino acids during ligand-receptor interaction. From structural and docking analyses, it is hypothesized that KMP11 of a specific Leishmania strain interacts with a specific anti-leishmanial drug candidate i.e. miltefosine interacts only with KMP11 of L. braziliensis but not with KMP11 of any other Leishmania strain. Highest docking score was found in case of pentamidine. Anticarcinogenic compound, sulphoraphane has shown comparable docking scores and H-bonds with KMP11 protein of six Leishmania strains.