Molecular Dynamics Simulation Study of the Structural Changes of Calcitonin in an Explicit Solvent

Abstract

Calcitonin is a 32 amino acids polypeptide hormone found in the osteoclast to lower the calcium and phosphorus level in different animals. This study employed molecular dynamics simulation technique to investigate the structural changes of calcitonin in an explicit solvent using the GROMACS 2016.5 software. The modeled structure of calcitonin was used during MD simulation using the Amber ff99-SB force field, TIP3P water model under isothermal-isobaric condition with periodic boundary condition imposed on x, y, z direction. The analyses were done using GROMACS software, grace and visual molecular dynamics (VMD) packages. The Root Mean Square Deviation (RMSD) Root Mean Square fluctuation (RMSF), hydrogen bonds and Radius of Gyration and end to end distance were computed from the reference initial structures. The RMSD values ranges from 0.5 nm to 1.5 nm during the simulation. The 6^th residue ( Thr) and 20^th ( His) residue has the lowest fluctuation at 0.4 nm. The RMSF values of the residues show that the polar residues tend to have a higher fluctuation than the hydrophobic residues with cysteine (1^st residue having the highest RMSF value of 0.8 nm and threonine 6^thresidue with the lowest RMSF value of 0.4 nm. Twenty-six intramolecular hydrogen bonds were found which indicates the stability of the protein during the simulation. Radius of gyration was computed to determine its compactness with water. The end to end distance of the protein decreases from 45.77 nm in the starting structure to 15.28 nm in the final MD structure and this indicates that the protein was undergoing folding during the simulation. From the RMSD, RMSF values, calcitonin tends to be relatively stable at a conformational state, the hydrogen bonds also supports its stability. The radius of gyration reveals it compactness with water and the end to end distance also supports its folding process.