| Institution: | 1. Key Laboratory of Molecular Medicine and Biotherapy in the Ministry of Industry and Information Technology, Department of Biology, School of Life Sciences, Beijing Institute of Technology, Beijing, China;2. State Key Laboratory of Membrane Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing, China
Tahir and Wu have equally contributed to the study.;3. Department of Biosciences, COMSATS University Islamabad, Sahiwal Campus, Islamabad, Pakistan;4. State Key Laboratory of Medicinal Chemical Biology, Key Laboratory of Bioactive Materials of Ministry of Education, College of Life Sciences, Nankai University, Tianjin, China;5. Pharmacy Department, Novomed Hospital, Dubai, UAE;6. Department of Bioinformatics and Biotechnology, International Islamic University Islamabad, Islamabad, Pakistan;7. Department of Biological Engineering/Institute of Biotransformation and Synthetic Biosystem, School of Life Sciences, Beijing Institute of Technology, Beijing, China;8. Departamento de Nutrición y Bioquímica, Facultad de Ciencias, Pontificia Universidad Javeriana, Bogotá, Colombia;9. King Fahd Medical Research Center, King Abdulaziz University, Jeddah, Saudi Arabia;10. State Key Laboratory of Membrane Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing, China |
| Abstract: | 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. |
