Computational Elucidation of Structural Basis for Ligand Binding withLeishmania donovaniAdenosine Kinase

Abstract

Enzyme adenosine kinase is responsible for phosphorylation of adenosine to AMP and is crucial for parasites which are purine auxotrophs. The present study describes development of robust homology model of Leishmania donovani adenosine kinase to forecast interaction phenomenon with inhibitory molecules using structure-based drug designing strategy. Docking calculation using reported organic small molecules and natural products revealed key active site residues such as Arg131 and Asp16 for ligand binding, which is consistent with previous studies. Molecular dynamics simulation of ligand protein complex revealed the importance of hydrogen bonding with active site residues and solvent molecules, which may be crucial for successful development of drug candidates. Precise role of Phe168 residue in the active site was elucidated in this report that provided stability to ligand-protein complex via aromatic-π contacts. Overall, the present study is believed to provide valuable information to design a new compound with improved activity for antileishmanial therapeutics development.

Phosphorylation of Translation Initiation Factor 2-Alpha in Leishmania donovani under Stress Is Necessary for Parasite Survival

“…mbi.ucla.edu/SAVES/), and the quality of the selected model was analyzed by using the ProSA-web server (45). The initial three-dimensional (3D) structure of the Leishmania donovani eIF2␣ protein obtained from homology modeling was optimized by using MD simulation according to a previously described protocol (46). The final MD was carried out for 20,000 ps (20 ns) with particle mesh Ewald (PME) electrostatics under NPT (N, amount of substance; P, pressure; T, temperature) conditions.…”

Retracted: Evaluating the immunomodulatory responses of LdODC‐derived MHC Class‐II restricted peptides against VL

“…Based on the prediction score and consensus nature, five epitopes were shortlisted for further analysis. To ensure its non‐homogeneity with the human proteome, BLASTP was performed against Homo sapiens …”

The Potential of Secondary Metabolites from Plants as Drugs or Leads against Protozoan Neglected Diseases—Part III: In-Silico Molecular Docking Investigations

“…Adenosine kinase is one of the enzymes in the purine salvage pathway, and Leishmania adenosine kinase is crucial for parasite survival [404]. Molecular docking (Glide, FlexX, GOLD) of a library of natural products with a homology-modeled structure of L. donovani adenosine kinase has revealed 1,6-digalloylglucose and lawsone ( Figure 13) as top hit phytochemical ligands [405].…”

“…natural products with a homology-modeled structure of L. donovani adenosine kinase has revealed 1,6-digalloylglucose and lawsone ( Figure 13) as top hit phytochemical ligands [405]. …”

“…These workers found ochrolifuanine A, chrobisiamone A, ailanthinone, korupensamine A, butyraxanthone B, ancistrolikokine A, calothwaitesixanthone, 7-deacetylkhivorin, 5-prenylbutein, methyl 6-hydroxyangolensate, and aulacocarpin A (Figure 14), to show notable docking energies (i.e., lower than the co-crystallized inhibitor WR99210). natural products with a homology-modeled structure of L. donovani adenosine kinase has revealed 1,6-digalloylglucose and lawsone ( Figure 13) as top hit phytochemical ligands [405]. …”