title: Computational elucidation of structural basis for ligand binding with Leishmania donovani adenosine 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.
authors.affiliation: Biomedical Informatics Centre, Rajendra Memorial Research Institute of Medical Science, Patna 800007, India
authors.forename: Rajiv K
authors.initials: RK
authors.lastname: Kar
authors.forename: Md Yousuf
authors.initials: MY
authors.lastname: Ansari
authors.forename: Priyanka
authors.initials: P
authors.lastname: Suryadevara
authors.forename: Bikash R
authors.initials: BR
authors.lastname: Sahoo
authors.forename: Ganesh C
authors.initials: GC
authors.lastname: Sahoo
authors.forename: Manas R
authors.initials: MR
authors.lastname: Dikhit
authors.forename: Pradeep
authors.initials: P
authors.lastname: Das
mesh_terms: D000248:Adenosine Kinase / Q000737:chemistry* / Q000378:metabolism*; D000595:Amino Acid Sequence; D006860:Hydrogen Bonding; D007893:Leishmania donovani / Q000201:enzymology*; D056004:Molecular Dynamics Simulation; D008969:Molecular Sequence Data; D015203:Reproducibility of Results; D040681:Structural Homology, Protein
chemical_list: D000248:Adenosine Kinase