Exploring the role of MC1R protein in Zebrafish Danio rerio by Molecular Modeling, Dynamics and Simulation Studies

The melanocortin-1 receptor protein (MC1R) is a G-protein-coupled receptor that plays an important role in anti-inflammatory and melanogenic activities, making it a promising therapeutic agent. Considering its functional diversity, we initially focus on predicting Zebrafish MC1R protein structure using EasyModeller v.4.0 to gain structural insights. Next, we describe the structure to highlight the importance of serine-threonine (ST) and aspartic acid-arginine-tyrosine (DRY) motifs, which are crucial for receptor activation and protein stability. Then, we demonstrate the molecular dynamics (MD) simulation of protein in an aqueous environment at 300 and 350 temperatures and present the trajectory analysis of receptor proteins in the dynamic system. We identify that the receptor protein had a significant conformational change with deviations at 300 K at 35 ps and 350 K at 55 ps, respectively. Notably, stability of the receptor protein was obtained at 300 K between 2.7 and 2.8 Å (400 and 600 ps) and at 350 K from 3.1 to 3.2 Å (400 and 600 ps), while this is the first report of the thermostability of the Zebrafish MC1R protein using MD as the main impact. Finally, we discuss how the receptor can be exploited as a therapeutic target for developing new peptides and drugs to improve skin pigmentation and treat pigmentary disorders.