Pharmacoinformatics and molecular docking reveal potential drug candidates against Schizophrenia to target TAAR6
| العنوان: | Pharmacoinformatics and molecular docking reveal potential drug candidates against Schizophrenia to target TAAR6 |
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| المؤلفون: | Hong Qing, Ghulam Md Ashraf, Hao Wu, Sheikh Arslan Sehgal, Seemab Amjad Fateh Khan, Naima Javed, Muhammad Saad Ahmed, George E. Barreto, Rana Adnan Tahir, Asif Mir, Anila Khalique |
| المصدر: | Journal of Cellular Physiology. 234:13263-13276 |
| بيانات النشر: | Wiley, 2018. |
| سنة النشر: | 2018 |
| مصطلحات موضوعية: | 0301 basic medicine, Drug, Protein Conformation, Physiology, media_common.quotation_subject, Pharmacoinformatics, Clinical Biochemistry, Aripiprazole, Cell Cycle Proteins, Computational biology, Receptors, G-Protein-Coupled, TAAR6, 03 medical and health sciences, 0302 clinical medicine, medicine, Humans, media_common, Virtual screening, Chemistry, Computational Biology, Cell Biology, Molecular Docking Simulation, 030104 developmental biology, Docking (molecular), Drug Design, 030220 oncology & carcinogenesis, Schizophrenia, Lipinski's rule of five, Pharmacophore, Antipsychotic Agents, medicine.drug |
| الوصف: | Schizophrenia (SZ) is a complex disabling disorder that leads to the mental disability and afflicts 1% of the world's total population and placed in top ten medical disorders. In current work, bioinformatics analyses were carried out on Trace amine (TA)-associated receptor 6 (TAAR6) to recognize the potential drugs and compounds against SZ. Comparative modeling and threading-based approaches were utilized for the structure prediction of TAAR6. Fifty-nine predicted structures were evaluated by various model assessment techniques and final model having only eight amino acids in the outlier region and 98.5% overall quality factor was chosen for further pharmacoinformatics and molecular docking analyses. From an extensive literature review, 11 Food and Drug Administration (FDA) approved drugs were analyzed by computational techniques and Aripiprazole was found as the most effective drug against SZ by targeting TAAR6. Here, we report five novel molecules which exhibited the highest binding affinity, effective drug properties, and interestingly, observed better results than the approved selected drugs against SZ by targeting TAAR6. The docking analyses revealed that Arg-92, Trp-98, Gln-191, Thr-192, Ala-290, Cys-291, Tyr-293, and Glu-294 residues were observed as critical interacting residues in receptor-ligand interactions. Absorption, distribution, metabolism, excretion, and toxicity (ADMET) properties, Lipinski rule of five, highest binding affinity coupled with virtual screening (VS), and pharmacophore modeling approach illustrated that aripiprazole (-8.6 kcal/mol) and TAAR6_0094 (-9.3 kcal/mol) are potential inhibitors for targeting TAAR6. It is suggested that schizophrenic patients have to use Aripiprazole for the medication of SZ by targeting TAAR6 and develop effective therapies by utilizing scrutinized novel compound. |
| تدمد: | 1097-4652 0021-9541 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::b2a39e9e2ef7a4efcbe47746e2828b40 https://doi.org/10.1002/jcp.27999 |
| حقوق: | CLOSED |
| رقم الأكسشن: | edsair.doi.dedup.....b2a39e9e2ef7a4efcbe47746e2828b40 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 10974652 00219541 |
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