应用ABEEMσπ/MM模型对重组人纤溶酶原Kringle 1结构域与配体分子的对接计算

高等学校化学学报 ›› 2010, Vol. 31 ›› Issue (8): 1630.

应用ABEEMσπ/MM模型对重组人纤溶酶原Kringle 1结构域与配体分子的对接计算

张文龙, 陈淑玲, 杨忠志

辽宁师范大学化学化工学院, 大连 116029

收稿日期:2009-12-11 出版日期:2010-08-10 发布日期:2010-08-10
通讯作者: 杨忠志, 男, 博士, 教授, 博士生导师, 主要从事理论与计算化学研究. E-mail: zzyang@lnnu.edu.cn
基金资助:
国家自然科学基金(批准号: 20633050)资助.

Calculation of Complexes of the Recombinant Kringle 1 Domain of Human Plasminogen and Its Ligands by ABEEMσπ/MM Method

ZHANG Wen-Long, CHEN Shu-Ling, YANG Zhong-Zhi*

School of Chemistry and Chemical Engineering, Liaoning Normal University, Dalian 116029, China

Received:2009-12-11 Online:2010-08-10 Published:2010-08-10
Contact: YANG Zhong-Zhi. E-mail: zzyang@lnnu.edu.cn
Supported by:
国家自然科学基金(批准号: 20633050)资助.

摘要/Abstract

摘要： 应用原子-键电负性均衡方法的浮动电荷分子力场(ABEEMσπ/MM), 对重组人纤溶酶原Kringle 1结构域(K1Pg)与配体ε-Aminocaproic acid(EACA), trans-4-(Aminomethyl) cyclohexane-1-carboxylic acid(AMCHA), L-Lysine(Lys), 7-Aminoheptanoic acid(7-AHA)和Benzylamine进行了半柔性对接计算. 用ABEEMσπ/MM模型优化得到的复合物K1Pg/EACA和K1Pg/AMCHA的结构很接近实验晶体结构. 此外通过对5种配体与K1Pg结合能的计算, 得出5种配体与K1Pg结合能的大小顺序为AMCHA>EACA>7-AHA>Lys>Benzy-lamine, 与实验中测得5种配体与K1pg的平衡结合常数K_a值大小顺序相一致.

关键词: ABEEMσπ浮动电荷分子力场, 重组人纤溶酶原Kringle 1结构域, 结合能, 氢键

Abstract: The semi-flexible docking studies were performed in order to understand the interaction between the recombinant Kringle 1 domain of human plasminogen and five ligands[ε-aminocaproic acid(EACA), trans-4-(aminomethyl) cyclohexane-1-carboxylic acid(AMCHA), L-lysine(Lys), 7-aminoheptanoic acid(7-AHA) and benzylamine] by means of ABEEMσπ/MM. The results show that the simulated structure is very close to the crystal structure. The calculated binding energies of the five complexes are in the order of AMCHA>EACA>7-AHA>Lys>Benzylamine, which is in agreement with the value of the equilibrium association constant(K_a) from experiment.

Key words: ABEEMσπ/MM method, Recombinant Kringle 1 domain of human plasminogen, Binding energy, Hydrogen bond

TrendMD:

张文龙, 陈淑玲, 杨忠志. 应用ABEEMσπ/MM模型对重组人纤溶酶原Kringle 1结构域与配体分子的对接计算. 高等学校化学学报, 2010, 31(8): 1630.

ZHANG Wen-Long, CHEN Shu-Ling, YANG Zhong-Zhi*. Calculation of Complexes of the Recombinant Kringle 1 Domain of Human Plasminogen and Its Ligands by ABEEMσπ/MM Method. Chem. J. Chinese Universities, 2010, 31(8): 1630.

参考文献

[1]Castellino F. J., McCance S. G.. Ciba. Found. Symp.[J], 1997, 212: 46—55 [2]Cao Y., Ji R. W., Davidson D., Schaller J., Marti D., Sohndel S., McCance S. G., O′Reilly M., Llinas M., Folkman J.. J. Biol. Chem.[J], 1996, 271: 29461—29467 [3]Marti D., Hu C. K., An S. S. A., von Haller P., Schaller J., Llinás M.. Biochemistry[J], 1997, 36: 11591—11604 [4]Chang Y., Mochalkin I., McCance S. G., Cheng B., Tulinsky A., Castellino F. J.. Biochemistry(Mosc)[J], 1998, 37(10): 3258—3271 [5]Lerch P. G., Rickli E. E.. Biochim. Biophys. Acta[J], 1980, 625: 374—378 [6]Mathews Ⅱ., Vanderhoff-Hanaver P., Castellino F. J., Tulinsky A.. Biochemistry[J], 1996, 35(8): 2567—2576 [7]CHU Hui-Ying(楚慧郢), ZHENG Qing-Chuan(郑清川), ZHAO Yong-Shan(赵勇山), ZHANG Hong-Xing(张红星). Chem. J. Chinese Universities(高等学校化学学报)[J], 2008, 29(12): 2398—2402 [8]Halgren T. A., Damm W.. Curr. Opin. Struct. Biol.[J], 2001, 11: 236—242 [9]CUI Bao-Qiu(崔宝秋), GUAN Qing-Mei(管清梅), GONG Li-Dong(宫利东), ZHAO Dong-Xia(赵东霞), YANG Zhong-Zhi(杨忠志). Chem. J. Chinese Universities(高等学校化学学报)[J], 2008, 29(3): 585—590 [10]Yang Z. Z., Wang C. S.. J. Phys. Chem. A[J], 1997, 101: 6315—6321 [11]Wang C. S., Yang Z. Z.. J. Chem. Phys.[J], 1999, 110: 6189—6197 [12]Cong Y., Yang Z. Z.. Chem. Phys. Lett.[J], 2000, 316: 324—329 [13]Yang Z. Z., Wu Y., Zhao D. X.. J. Chem. Phys.[J], 2004, 120: 2541—2557 [14]Zhang Q., Yang Z. Z.. Chem. Phys. Lett.[J], 2005, 403: 242—247 [15]Li X., Yang Z. Z.. J. Chem. Phys.[J], 2005, 122: 084514-1—084514-15 [16]Yang Z. Z., Li X.. J. Chem. Phys.[J], 2005, 123: 094507-1—094507-10 [17]Yang Z. Z., Zhang Q.. J. Comput. Chem.[J], 2006, 27: 1—10 [18]Yang Z. Z., Qian P.. J. Chem. Phys.[J], 2006, 125: 064311-1—064311-16 [19]Zhang Q., Yang Z. Z.. Acta Phys. Chim. Sin.[J], 2006, 22: 1243—1247 [20]LIU Cui(刘翠), YANG Zhong-Zhi(杨忠志). Journal of Molecular Science(分子科学学报)[J], 2009, 25: 231—234 [21]LIU Cui(刘翠), YANG Zhong-Zhi(杨忠志). Science in China, Series B(中国科学, B辑)[J], 2009, 39: 1461—1468 [22]Kaminski G. A., Friesner R. A., Tirado-Rives J., Jorgensen W. L.. J. Phys. Chem. B[J], 2001, 105: 6474—6487