Investigation on Bioactive Protective Function of Amino Acids to Insulin by Molecular Simulation_Journal of Biomedical Engineering

Authors：

 LIDaixi ¹ , ZHAIZhen ¹ , GUOBaisong ² , LIUBaolin ¹ , ZHANGYan ¹ , YUHuaxing ¹ , LIULi ¹ , YANGChunsheng ²

1. Institute of Biothermal Engineering, University of Shanghai for Science and Technology, Shanghai 200093, China;
2. Lyophilization Laboratory, Shanghai Tofflon Science and Technology Co., Ltd. Shanghai 201108, China;

Corresponding author：

LIDaixi, Email: dxli75@126.com

Keywords：

amino acid; human insulin; desiccation; bioactive protection; molecular simulation

DOI：

10.7507/1001-5515.20140154

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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.

Citation： LIDaixi, ZHAIZhen, GUOBaisong, LIUBaolin, ZHANGYan, YUHuaxing, LIULi, YANGChunsheng. Investigation on Bioactive Protective Function of Amino Acids to Insulin by Molecular Simulation. Journal of Biomedical Engineering, 2014, 31(4): 822-826. doi: 10.7507/1001-5515.20140154 Copy

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1. KIDRON M, MIZRACHI Y, BARON H, et al. New oral formulation of human insulin[J]. Diabetes, 2001, 50: A439-A439.
2. KLING J. Dreamboat sinks prospects for fast approval of inhaled insulin[J]. Nat Biotechnol, 2011, 29(3): 175-176.
3. VAN DER SPOEL D, LINDAHL E, HESS B, et al. GROMACS: fast, flexible, and free[J]. J Comput Chem, 2005, 26(16): 1701-1718.
4. ZHOU R. Replica exchange molecular dynamics method for protein folding simulation[J]. Methods Mol Biol, 2007, 350: 205-223.
5. TUNNACLIFFE A, WISE M J. The continuing conundrum of the LEA proteins[J]. Naturwissenschaften, 2007, 94(10): 791-812.
6. STOCKER U, VAN GUNSTEREN W F. Molecular dynamics simulation of hen egg white lysozyme: a test of the GROMOS96 force field against nuclear magnetic resonance data[J]. Proteins, 2000, 40(1): 145-153.
7. PASCHEK D, DAY R, GARCÍA A E. Influence of water-protein hydrogen bonding on the stability of Trp-cage miniprotein. A comparison between the TIP3P and TIP4P-Ew water models[J]. Phys Chem Chem Phys, 2011, 13(44): 19840-19847.
8. BUSSI G, ZYKOVA-TIMAN T, PARRINELLO M. Isothermal-isobaric molecular dynamics using stochastic velocity rescaling[J]. J Chem Phys, 2009, 130(7): 074101-074109.
9. WANG H, DOMMERT F, HOLM C. Optimizing working parameters of the smooth particle mesh Ewald algorithm in terms of accuracy and efficiency[J]. J Chem Phys, 2010, 133(3): 034117-034128.
10. KRISHNA N R, PATTABHI V, RAJAN S S. Metal induced conformational changes in human insulin: crystal structures of Sr²⁺, Ni²⁺ and Cu²⁺ complexes of human insulin[J]. Protein Pept Lett, 2011, 18(5): 457-466.
11. GOLOVINA E A, GOLOVIN A, HOEKSTRA F A, et al. Water replacement hypothesis in atomic details: effect of trehalose on the structure of single dehydrated POPC bilayers[J]. Langmuir, 2010, 26(13): 11118-11126.

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