Inhibition of the peptide translated from circPPP1R12A by Myricetin and its possible implication: An in-silicoapproach

Abstract Abstract: CircPPP1R12A translates a unique seventy-two amino acid long peptide that is involved in the onset and progression of colon carcinoma by engaging itself in Mst pathway. The possible interaction of the peptide with Mst1/2 proteins can disrupt the activation of this pathway leading to abrupt cell proliferation. Myricetin, a natural flavonoid molecule, has been evaluated as a possible ligand for the peptide. The binding affinity of Myricetin towards the peptide was investigated through molecular docking and MD simulation studies. Molecular docking studies proposed that thirteen amino acid residues of the peptide were found to interact with Myricetin to bind to it. Different attributes of the dynamics simulation data further revealed that the interplay between Myricetin and the peptide could stabilize the binding. In-silico mutagenesis studies indicated that His40, Phe41, Arg43 and His46 are pivotal for the binding of the peptide to Myricetin. These residues were also taking part in the Mst1/2-peptide complex formation. The interaction of the peptide with the Mst proteins possibly deactivates the Mst pathway hence binding of Myricetin can prevent this deactivation. As a naturally occurring flavonoid, it could be a potentially beneficial dietary compound with therapeutic advantage against colon cancer.