International Journal of Pharma and Bio Sciences MODELING AND DOCKING STUDIES OF 4-AMINOBUTYRATE AMINOTRANSFERASE FOR HUNTINGTON’S DISEASE
نویسندگان
چکیده
Huntington’s disease (HD) is a neurodegenerative disease and 4-aminobutanoic acid (GABA) is an inhibitory neurotransmitter in mammalian nervous system which regulates muscle tone of the body. GABA acts at inhibitory synapses in the brain by binding to specific transmembrane receptors in the plasma membrane of both preand postsynaptic neuronal processes. γ-Aminobutyrate aminotransferase (GABA-AT) degrades the inhibitory neurotransmitter GABA. GABA-AT, a pyridoxal-dependent enzyme, is a target for antiepileptic and several other serious neuroactive drugs including drugs for Huntington’s disease. Hence, its selective inhibition raises concentrations of GABA in brain. Defects in GABA-T cause accumulation of beta-alanine and gamma aminobutyric acid in plasma and spinal fluid, as well as accumulation of homocarnosine in spinal fluid. Symptoms include hyperreflexia, hypotonia, lethargia, macrosomia, mental retardation, and siezures. Therefore, GABA-AT is the preferential choice for inhibition to increase the concentration of GABA in brain. Therefore, an attempt was made to obtain the suitable inhibitors of GABA-AT by de novo creation of structurally flattering lead molecules which were further validated by docking analysis with GABA-AT protein. The screening of these results revealed that ( 2 S)3 [( 3aR, 4S, 6R, 7aS) 6 methyloctahydro1 H inden 4 yl] -2(propanoylamino)propanoic acid was found as the best fit over Lipinski’s rule of five and other ADME parameters.
منابع مشابه
Modelface: an application programming interface (API) for homology modeling studies using Modeller software
An interactive application, Modelface, was presented for Modeller software based on windows platform. The application is able to run all steps of homology modeling including pdb to fasta generation, running clustal, model building and loop refinement. Other modules of modeler including energy calculation, energy minimization and the ability to make single point mutations in the PDB structures a...
متن کاملDiscovery of Novel Glucagon Receptor Antagonists Using Combined Pharmacophore Modeling and Docking
Glucagon and the glucagon receptor are most important molecules control over blood glucose concentrations. These two molecules are very important to studies of type 2 diabetic patients. In literature, several classes of small molecule antagonists of the human glucagon receptor have been reported. Glucagon receptor antagonist could decrease hepatic glucose output and improve glucose control in d...
متن کاملModelface: an application programming interface (API) for homology modeling studies using Modeller software
An interactive application, Modelface, was presented for Modeller software based on windows platform. The application is able to run all steps of homology modeling including pdb to fasta generation, running clustal, model building and loop refinement. Other modules of modeler including energy calculation, energy minimization and the ability to make single point mutations in the PDB structures a...
متن کاملMathematical Modeling and Release Kinetics of Green Tea Polyphenols Released from Casein Nanoparticles
Drug release kinetics plays an important role in determining the mechanism of drug release, which in turn helps in formulating controlled/sustained release formulations.In our study, different concentrations of green tea polyphenols (GTP) were encapsulated into casein nanoparticles which showed a maximum encapsulation efficiency (76.9%) at a GTP concentration of 5 mg/mL. The casein nanopa...
متن کاملMathematical Modeling and Release Kinetics of Green Tea Polyphenols Released from Casein Nanoparticles
Drug release kinetics plays an important role in determining the mechanism of drug release, which in turn helps in formulating controlled/sustained release formulations.In our study, different concentrations of green tea polyphenols (GTP) were encapsulated into casein nanoparticles which showed a maximum encapsulation efficiency (76.9%) at a GTP concentration of 5 mg/mL. The casein nanopa...
متن کامل