Computational Elucidation of Structural Basis for Ligand Binding with Leishmania donovani Adenosine Kinase.

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 molecul...

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Publicado en:BioMed Research International Vol. 2013; pp. 609289 - 609290
Autores principales: Kar, Rajiv K, Ansari, Md Yousuf, Suryadevara, Priyanka, Sahoo, Bikash R, Sahoo, Ganesh C, Dikhit, Manas R, Das, Pradeep
Formato: research Journal Article
Publicado: Wiley-Blackwell 2013
Acceso en línea:Ver este registro en EBSCOhost
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      pub: Wiley-Blackwell
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        atl: Computational Elucidation of Structural Basis for Ligand Binding with Leishmania donovani Adenosine Kinase.
      aug:
        au:
          Kar, Rajiv K
          Ansari, Md Yousuf
          Suryadevara, Priyanka
          Sahoo, Bikash R
          Sahoo, Ganesh C
          Dikhit, Manas R
          Das, Pradeep
        affil: Biomedical Informatics Centre, Rajendra Memorial Research Institute of Medical Science, Patna 800007, India ; Department of Pharmacoinformatics, National Institute of Pharmaceutical Education and Research (NIPER), Hajipur 844102, India.
      sug:
        subj:
          Transferases
          Transferases Metabolism
          Leishmania
          Computer Simulation
          Amino Acids
          Chemistry, Physical
          Documentation
          Reproducibility of Results
          Proteins
          Human
      ab: 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 ligandprotein complex via aromatic-re contacts. Overall, the present study is believed to provide valuable information to design a new compound with improved activity for antileishmanial therapeutics development.
      pubtype: Academic Journal
      doctype:
        research
        Journal Article
      ougenre: Article
    language: English
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