An In-Silico Approach for Designing a Potential Antagonistic Molecule Targeting β2-adrenoreceptor Having Therapeutic Significance

One of the largest families of membrane proteins, the G protein-coupled receptors (GPCRs) has been a very important target of drug discovery as they are involved in having a regulatory role in a variety of signaling pathways at the cellular level in response to external stimuli. Modern in-silico and crystallographic approaches have further made it easier to peep into their structures. In this study, β2 adrenergic receptor (β2AR) has been targeted, and a new ligand molecule using the de-novo approach has been proposed. Using 1-Amino-3-(2,3-dihydro-1H-indol-4-yloxy)-propan-2-ol, the best fitting binding fragments were established with a significant dissociation constant value of 5-7 nanomolar. The flexibility of specific active sites was also investigated, and it was observed that residues 114 (V), 117 (V), 203 (S), 286 (W), and 289 (F) played a crucial role in accommodating ligand for the best binding. Upon examination of the bioavailability parameters, the ligand var9 exhibited significant inhibitory characteristics having lower toxicity values and high drug likeliness properties. Findings certainly hold significance in terms of targeting GPCRs in getting insight into structure-based drug designing and drug discovery.