In silico strategy for detailing the binding modes of a novel family of peptides proven as ghrelin receptor agonists

Computational Investigation of the Impact of the Ghrelin Hormone Gene Variation (R51q) on the Hormone-receptor Binding Pattern

“…The active site residues/ binding residues were highlighted and submitted to the docking server based on previously published studies. 3,8,12,20,21 According to the cited studies, the binding residues for the receptor included: D99, R102, Y106, Q120, S123, E124, E197, R199, F279, F286, F290, Q302, N305, F309, F312, and Y313. On the other hand, the active part of the ligand was the N-terminal rejoin only due to the C-terminal part is functionally inactive.…”

“…The MD simulations were applied with the following parameters: a force field of charmm36, a solvent box size of 10*10*10 nm, 0.15 M of Na + and Clions, 310 K of temperature, and a time constant of 100 ns due to a recently published study. 8 Moreover, the rest of the MD simulation steps, including minimization, equilibration, and production steps have been done manually via GROMACS command lines.…”

“…6 Moreover, it has cardiovascular effects, protects against ischemia/reperfusion injury in the heart, has anti-inflammatory properties, and reduces antioxidant stress in a variety of diseases. 7,8 It appears that the structure and functions of ghrelin hormone are highly conserved in vertebrates. It is the endogenous ligand of the growth hormone secretagogue receptor (GHSR) , a class A, G protein-coupled receptor (GPCR) that induces calcium mobilization, identified in pigs, humans, teleosts, and birds.…”

“…It is the endogenous ligand of the growth hormone secretagogue receptor (GHSR) , a class A, G protein-coupled receptor (GPCR) that induces calcium mobilization, identified in pigs, humans, teleosts, and birds. 8,9 This receptor has two alternative splice variants: GHS-R1a, the active receptor that mediates the biological actions of growth hormone secretagogues (GHS) and ghrelin, and GHS-R1b, an inactive receptor with the first 5 transmembrane helices that regulate the expression of GHSR1a at the cell surface. 10 To activate its receptor, ghrelin requires the acylation of a fatty acid (octanoyl or decanoyl) to its serine 3 residue, a modification carried out by the enzyme ghrelin-o-acyltransferase (GOAT).…”

“…Previous computational approach studies about ghrelin hormone and its receptor GHSR-1a have focused on their binding pattern, but none have investigated their gene mutation impacts and how these gene variations could alter the binding pattern and their final structures. 3,8,12,20,21 Thus, the current study focused on the impact of R51Q variation on the ghrelin hormone and how this amino acid substitution could alter the hormone-receptor binding pattern.…”