Molecular modeling and docking on the 5HT1A receptor with small molecule drugs used in bipolar Disorder
1Ajay Mahant, 2Preeti Mishra and 3*Rohit Seth
1,3Cell Biology and Neuroscience Laboratory Department of Zoology, School of Life Sciences Guru Ghasidas Vishwavidyalaya (A Central University) Bilaspur-495009 (India) Email:ajaymahantggu@gmail.com 2Sickle Cell Institute, Raipur-492001 (India) Email: preetimishra1219@gmail.com ORCID ID – 0000-0001-5729-6197 Email: rohitseth123@gmail.com *Address for correspondence
ABSTRACT
Bipolar Disorder is a primary mental condition marked by recurrent episodes of manic and depressive states that affect thought, emotion, and social behaviour. It is a bipolar illness caused by periods of depression, mania, mixed mania, and hypomania. 5HT1A receptors are found in presynaptic and postsynaptic regions of neurons— anxiolytic, antidepressant, and antipsychotic medications work by activating this receptor. Serotonin receptors are proteins that play a role in various neurological and biological processes, including mood, sleep, hunger, cognition, learning, and memory. The aim of this current work Molecular docking analysis was used in this study to examine how 5-HT1A receptors are affected by antipsychotics and antidepressants in the case of bipolar disorder. This study was based on molecular docking using different tools for analyzing ligands-receptor interactions. There are many types of software included in molecular dockings, like Iterative Threading Assembly Refinement (I-TASSER), Discover Studio Visualizer, Schrodinger, Protein Structure Analysis (ProSA), SiteMap program, Swiss ADME online software, and Mol Inspiration software etc. 5-HT1A receptors are frequently linked to drug usage and addiction since they are a famous target population for various pharmaceutical and recreational drugs. We are using Iterative Threading Assembly Refinement (I-TASSER) software, and Discover Studio Visualizer was used to model the 5HT1A protein in this investigation. The protein preparation was used to add hydrogen to the simulated structure and improve the protonation states of the LYS, ASP, and PHE residues. The sitemap function of the Schrodinger package was used to determine the active site of the modeled protein. We also used Glide to conduct docking tests with various ligands retrieved from the PubChem database. Potential ligands have been assessed, and their interactions with 5HT1A were discovered based on glide scores. The top hits were further examined for drug-likeliness according to Lipinski’s rule, bioactivity rating, and ADME characteristics. The 5HT1A receptor protein was selected for the study because it has been suggested to be an appropriate target for the critical analysis. As a result, we present two compounds, risperidone and cariprazine, that successfully met all in silico criteria, requiring more in vitro and in vivo research. In the future, this work could be helpful in the drug design and development of novel and potentially effective 5HT1A inhibitors. Further, this study is expected to help create more specific and individualized treatment approaches for patients with bipolar disorder