Genetic mutations in cannabis receptors could be fixed with new therapeutic peptide

Cannabinoid receptors 1 and 2 (CNR1 and CNR2) play an important role in the endocannabinoid system and intracellular pathways. Their beneficial effects became destroyed in the event of some mutation. Identifying protective drugs for mutation is highly necessary to eliminate its destruction. The research aims to understand the role of chimeric peptides in CNR1 and CNR2 nsSNPs. The research objectives are to find destructive nsSNPs through in-silico prediction and protein-only state molecular dynamics simulation. To understand the role of chimeric peptides on interaction with nsSNPs through docking analysis and protein-ligand state molecular dynamics simulation. To validate in-silico findings through in-vitro cell expression experiments. The research methods involved 36 in-silico online prediction tools, simulation for 100 ns, 29 trajectory analysis modules, three docking programs, and western blotting techniques. Four CNR1 and six CNR2 nsSNPs were shortlisted as destructive nsSNPs using in-silico tools. Further, CNR1 N134T and CNR2 I298N nsSNPs were shortlisted as highly destructive nsSNPs using simulation and docking analysis. Beneficial peptides were shortlisted using docking analysis and simulation with wild type. This research found that the chimeric peptide MP-13 has the best binding affinity and dynamics properties with wild-type and nsSNPs. It also almost restores dynamics properties and improves binding affinity in nsSNPs. It is most effective in influencing CNR1 and CNR2 signaling responses despite nsSNPs. Based on in-silico and in-vitro analysis, the research concludes that MP-13 has the strongest effect on CNR1 and CNR2 nsSNPs. The workflow of the present research is represented in a graphical illustration.