[Molecular simulation research on aggregation of insulin].
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.
School of Medical Instrument and Food Engineering, University of Shanghai for Science and Technology, Shanghai 200093, China. dxli75@126.com
Daixi
D
Li
School of Medical Instrument and Food Engineering, University of Shanghai for Science and Technology, Shanghai 200093, China.
Baolin
B
Liu
Institute of Lyophilization Technology, Shanghai Tofflon Science and Technology Co. Ltd., Shanghai 201108, China.
Baisong
B
Guo
School of Medical Instrument and Food Engineering, University of Shanghai for Science and Technology, Shanghai 200093, China.
Yaru
Y
Liu
School of Medical Instrument and Food Engineering, University of Shanghai for Science and Technology, Shanghai 200093, China.
Zhen
Z
Zhai
School of Medical Instrument and Food Engineering, University of Shanghai for Science and Technology, Shanghai 200093, China.
Yan
Y
Zhang
Department of Chemistry, National Sun Yat-Sen University, Kaohsiung, Taiwan 80424, China.
Chenglung
C
Chen
Department of Biochemistry and Molecular Biology, Shanghai Medical College, Fudan University, Shanghai 200032, China.
Shanlin
S
Liu
D007328:Insulin / Q000737:chemistry* / Q000378:metabolism*; D056004:Molecular Dynamics Simulation; D055550:Protein Stability; D015032:Zinc / Q000737:chemistry
D007328:Insulin; C034329:insulin dimers; D015032:Zinc