The gastrointestinal system produces diverse peptide hormones, including a 22-amino acid long human motilin which is essential for initiating inner digestive migratory contractions interacts directly with receptors on gastrointestinal smooth muscle cells. This interaction is a focal point for potential drug targeting in gastrointestinal disorders. The modulation of gastrointestinal motility through motilin-receptor interplay presents a promising avenue for therapeutic interventions. This study aims to elucidate the molecular interactions between a motilin and its cognate receptor. The 3D structure of motilin hormone was obtained in purified form from the PDB database, while the unavailable motilin receptor structure was homology-modeled using I-TASSER. Validation and quality checks were performed using ERRAT and Procheck while physiochemical properties were predicted with ProtParam and both, motilin and its receptor, underwent energy minimization on Galaxy Refine for subsequent docking studies on Cluspro online server. Next docking was validated with an RC plot, and analyzed for interaction studies on PDBsum and PDBePisa.. The motilin receptor model demonstrated structural stability, supported by an 86% ERRAT score and 95.5% of residues within the favored regions of the Ramachandran plot. Docking analysis yielded a stable complex with 7 hydrogen bonds and 1 disulphide linkage, validating the study's integrity. This in silico studies of motilin with its receptor, provides a reliable foundation for further functional, structural, and therapeutic investigations, suggesting potential avenues for designing motilin analogues to design motilin-related disorders.

Keywords: Motilin, in silico analysis, GI disorder, docking