A Study Of Insulin Hexamer By Molecular Dynamics Simulations

Molecular dynamics (MD) simulation has become an extremely powerful tool not only to understand and interpret the experiments at the microscopic level, but also to study regions which are not accessible experimentally or imply very expensive experiments. The result of MD simulations is also very useful not only to understand the essential process and nature of life phenomena at the atomic and molecular level, but also to understand the biological function and interactions between proteins.In order to study the flexibility and stability of insulin hexamer in solution and the role of Zn2+ and phenol, two 600 ps MD simulations of the R-state human insulin hexamer system were carried out respectively. The two MD simulations were carried out with the GROMOS96 package and its force field. The MD simulation data were analyzed in terms of average atomic positions, root mean square (RMS) fluctuations, monomer-monomer interactions, hydrogen bond (H-bond) network, secondary structure, and so on. Through the comparison, we found that when the system includes Zn2+ ions and phenol, the stability of insulin hexamer is enhanced, but the conformational flexibility related to its biological activity is decreased. In addition, the insulin hexamer tends to dissociate in the absence of Zn2+ and phenol.These simulation results agree well with the experimental data, which deepen and increase our understanding of essential properties of the insulin molecules, and provide a basis for the rational design of insulin pharmaceutical preparations.