Using Homology Modeling, Molecular Dynamics and Molecular Docking Techniques to Identify Inhibitor Binding Regions of Somatostatin Receptor 1

doi:10.1007/s40242-013-2103-1

Abstract

Abstract:

The G protein coupled receptor(GPCR), one of the members in the superfamily, which consists of thousands of integral membrane proteins, exerts a wide variety of physiological functions and responses to a large portion of the drug targets. The 3D structure of somatostatin receptor 1(SSTR1) was modeled and refined by means of homology modeling and molecular dynamics simulation. This model was assessed by Verify-3D and Vadar, which confirmed the reliability of the refined model. The interaction between the inhibitor cysteamine, somatostatin(SST) and SSTR1 was investigated by a molecular docking program, Affinity. The binding module not only showed the crucial residues involved in the interaction, but also provided important information about the interaction between SSTR1 on the one hand and ligands on the other, which might be the significant evidence for the structure-based design.

Key words: Somatostatin receptor 1, Homology modeling, Docking

LAN Hai-nan, WANG Yue-xi, ZHENG Ming-zhu, HAN Wei-wei, ZHENG Xin. Using Homology Modeling, Molecular Dynamics and Molecular Docking Techniques to Identify Inhibitor Binding Regions of Somatostatin Receptor 1[J]. Chemical Research in Chinese Universities, 2013, 29(1): 139-143.

References

[1] Zhong C., Ding J., Acta Biochim. Biophys. Sin., 2011, 43, 337

[2] Wu B. L., Chien E. Y. T., Mol C. D., Fenalti G., Liu W., Katritch V., Abagyan R., Brooun A., Wells P., Bi C. F., Hamel D. J., Kuhn P., Handel T. M., Cherezov V., Stevens R. C., Science, 2010, 330, 1066

[3] Baggiolini M., Nature, 1998, 392, 565

[4] Moser B., Wolf M., Walz A., Loetscher P., Trends Immunol., 2004, 25, 75

[5] Mackay C. R., Nat. Immunol., 2001, 2, 95

[6] Congreve M., Marshall F., Br. J. Pharmacol., 2010, 159, 986

[7] Watt H. L., Kharmate G. D., Kumar U., Cell Signal., 2009, 21, 428

[8] Zatelli M. C., Piccin D., Tagliati F., Ambrosio M. R., Margutti A., Padovani R., Scanarini M., Culler M. D., degli Uberti E. C., J. Clin. Endocrinol. Metab., 2003, 88, 2797

[9] Liapakis G., Tallent M., Reisine T., Metabolism, 1996, 45, 12

[10] Reynisdottir I., Massagué J., Genes. Dev., 1997, 11, 492

[11] Altschu S. F., Madden T. L., Sch?ffer A. A., Zhang J., Zhang Z., Miller W., Lipman D. J., Nucleic. Acid Res., 1997, 25, 3389

[12] Marklund S., Tuggle C. K., Rothschild M. F., Anim. Genet., 2000, 31, 318

[13] Schwede T., Kopp J., Guex N., Peitsch M. C., Nucleic. Acids Res., 2003, 31, 3381

[14] Guex N., Peitsch M. C., Electrophoresis, 1997, 18, 2714

[15] Arnold K., Bordoli L., Kopp J., Schwede T., Bioinformatics, 2006, 22, 195

[16] Zhan D., Han W. W., Feng Y., J. Mol. Model., 2011, 17, 1241

[17] Kiefer F., Arnold K., Künzli M., Bordoli L., Schwede T., Nucleic. Acids Res., 1995, 37, D387

[18] Arnold K., Bordoli L., Kopp J., Schwede T., Bioinformatics, 2006, 22, 195

[19] Gruber C. C., Pleiss J., J. Comput. Chem., 2011, 32, 600

[20] Jorgensen W. L., Chandrasekhar J., Madurs J., Impey R. W., Klein M. L., J. Chem. Phys., 1983, 79, 926

[21] Binding Site Analysis User Guide, Accelrys Inc., San Diego, 1999

[22] Dundas J., Zheng O., Tseng J., Binkowski A., Turpaz Y., Liang Y., Nucleic. Acids Res., 2006, 34, W116

[23] Trott O., Olson A.J., J. Comput. Chem., 2010, 31, 455

[24] Affinity User Guide, Accelrys Inc., San Diego, 1999

[25] Han W. W., Zhan D. L., Zhao X., Wang S., Chem. Res. Chinese Universities, 2010, 26(1), 128

[26] Han W. W., Wang Y., Luo Q., Feng Y., J. Chem. Theory. Comput., 2011, 10, 165

[27] Han W. W., Zhou Y. H., Luo Q., Yao Y., Li Z. S., Polymer, 2007, 48, 3726

[28] Han W. W., Wang Y., Zhou Y. H., Yao Y., Li Z. S., Feng Y., J. Mol. Model., 2009, 15, 481