Molecular Dynamics Simulation of Β-Melanotropin Stimulating Hormone (Β-MSH) Docked Onto the Receptor MC4R.

Melanocortin system is composed of four peptide hormones known as α, β, γ and adrenocorticotropic hormone (ACTH), derived from post-translational cleavage of a polypeptide precursor ‘proopiomelanocortin (POMC)’. Among these hormones; β-melanotropin stimulating hormone (β-MSH), an 18 amino acid residue peptide fragment is an important hormone as it is involved in activation of MC4R to induce lean phenotype ‘balance between energy intake and energy expenditure’. In addition to this, MC4R is also involved in the modulation of erectile function, including the spinal cord and pelvic ganglion of rats and the penis of both rats and humans, providing an anatomical basis for melanocortin effects on sexual function. MC4R is one of the five melanocortin receptors (MC1R–MC5R) which have been characterized with tissue-specific expression patterns and different binding affinities for each of the melanocortin hormones to regulate various biological functions. In the present work, 3D models of MC4R and β-MSH have been predicted, followed by docking and molecular dynamics simulation. While the 3D model of MC4R receptor has been predicted through threading approach, structure of β- MSH was built based on ab initio technique. The β-MSH model was later successfully docked onto the MC4R protein. Molecular dynamics (MD) simulation for 15 ns was used to compute the electrostatic solvation energy as well as binding energy between MC4R with β-MSH model under implicit solvent conditions.