Homology modeling of adenosine A2A receptor and molecular docking for exploration of appropriate potent antagonists for treatment of Parkinson's disease.
Parkinson's disease (PD) is a neurodegenerative disorder of central nervous system (CNS) that impaired the patient motor skills, speech and other functions. Adenosine A2A receptors have a unique cellular distribution in the neuron, which is used as a potential target for PD. Homology modeling was used to construct the 3-D structure of A2A using the known template (PDB: 2VT4), and the stereochemical quality was validated. Several effective antagonist drugs were selected and active amino acid residues in A2A were targeted on the basis of robust binding affinity between protein-drug interactions in molecular docking. Six antagonists, Bromocriptine, Cabergoline, Etilevodopa, Lysuride, Melevodopa and Pramipexole, were found more potent for binding and the active amino acids residues were identified (http://www.rcsb.org/pdb/) in A2A receptor. It could be used as the basis for rationale designing of novel antagonist drugs against Parkinson's disease.
Singh
Vijai
V
Bioinformatics Centre, Biotech Park, Lucknow, India.
Somvanshi
Pallavi
P
D058917:Adenosine A2 Receptor Antagonists; D000595:Amino Acid Sequence; D000978:Antiparkinson Agents / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D001665:Binding Sites; D017076:Computer-Aided Design; D030541:Databases, Genetic; D015195:Drug Design; D006801:Humans; D021621:Imaging, Three-Dimensional; D008958:Models, Molecular; D008969:Molecular Sequence Data; D015394:Molecular Structure; D011487:Protein Conformation; D043683:Receptors, Adenosine A2 / Q000737:chemistry / Q000378:metabolism; D015203:Reproducibility of Results
D058917:Adenosine A2 Receptor Antagonists; D000978:Antiparkinson Agents; D043683:Receptors, Adenosine A2