Investigation on bioactive protective function of amino acids to insulin by molecular simulation / 生物医学工程学杂志

Heat sensitive protein medicines are increasingly exhibiting their critical importance on treatment of various diseases at present. But their popularization and application meet a great challenge because of their heat instability. In the present study, insulin was taken as a heat sensitive protein medicine and amino acid as bio-protective agent in order to investigate if these amino acids can protect the insulin from losing its bioactivity due to desiccation. The experiment was performed by using replica exchange molecular simulation (REMD) method and Gromacs software with Gromos96 (53a6) force field. The REMD results indicated that these amino acids could protect the bioactive structure of insulin during desiccation. The configurations of the protected insulin were preserved very well. Those results proved that amino acid is a kind of good bioactive protective agent for the heat sensitive protein medicines.

Investigation on bioactive protection of LEA protein for insulin by molecular simulation in the low-temperature drying process / 生物医学工程学杂志

Nowadays various protein medicines are increasingly playing significant roles in the treatment of many diseases, but the bioactive structures of such kinds of protein medicines are unstable because they are heat sensitive. Therefore, it is very important to explore a protective method and to explain the protective mechanism of protein medicines. In the present research, insulin was chosen as a heat-sensitive protein medicine, and a Group 3 late embryogenesis abundant (LEA) protein was chosen as its bioactive protectant during desiccation. The results of replica exchange molecular dynamics simulation suggest that comparing with insulin without any protection, the bioactive 3D structure and secondary structure of the insulin protected by LEA protein were preserved very well. All analyzing results proved that the LEA protein was a good bioactive protectant for heat sensitive protein medicines.

Molecular simulation research on aggregation of insulin / 生物医学工程学杂志

In the present research, molecular simulation and quantum chemistry calculations were combined to investigate the thermal stability of three kinds of insulin aggregations and the effect of Zn (II) ion coordination on these aggregations. The results of molecular simulation indicated that the three insulin dimers in the same sphere closed hexamer had synergistic stability. It is the synergistic stability that enhances the structural and thermal stability of insulin, preserves its bioactivity during production, storage, and delivery of insulin formulations, and prolongs its halflife in human bodies. According to the results of quantum chemistry calculations, each Zn (II)-N (Im-insulin) bond energy can reach 73.610 kJ/mol for insulin hexamer and 79.907 kJ/mol for insulin tetramer. However, the results of Gibbs free energy changes still indicats that the coordination of zinc (II) ions is unfavorable for the formation of insulin hexamer, because the standard Gibbs free energy change of the coordinate reaction of zinc (II) ions associated with the formatting insulin hexamer is positive and increased.