渗透剂的分子体积和极性表面积分率对胰凝乳蛋白酶抑制剂2热稳定性的影响

doi:10.3866/PKU.WHXB20101011

物理化学学报 >> 2010, Vol. 26 >> Issue (10): 2813-2820.doi: 10.3866/PKU.WHXB20101011

渗透剂的分子体积和极性表面积分率对胰凝乳蛋白酶抑制剂2热稳定性的影响

刘夫锋, 纪络, 董晓燕

天津大学化工学院生物化工系, 天津 300072;
天津大学系统生物工程教育部重点实验室, 天津 300072

收稿日期:2010-06-28 修回日期:2010-07-19 发布日期:2010-09-27
通讯作者: 董晓燕 E-mail:d_xy@tju.edu.cn
基金资助:
国家自然科学基金(20636040, 20876111, 20906068), 国家重点基础研究发展规划项目(973) (2009CB724705), 天津市科委自然科学重点基金(08JCZDJC17100) 和天津大学自主创新基金资助

Effects ofMolecular Volume and Fractional Polar Surface Area of Osmolytes on the Thermal Stability of Chymotrypsin Inhibitor 2

LIU Fu-Feng, JI Luo, DONG Xiao-Yan

Department of Biochemical Engineering, School of Chemical Engineering and Technology, Tianjin University, Tianjin 300072, P. R. China; Key Laboratory of Systems Bioengineering, Ministry of Education, Tianjin University, Tianjin 300072, P. R. China

Received:2010-06-28 Revised:2010-07-19 Published:2010-09-27
Contact: DONG Xiao-Yan E-mail:d_xy@tju.edu.cn
Supported by:
The project was supported by the National Natural Science Foundation of China (20636040, 20876111, 20906068), National Key Basic Research Program of China (973) (2009CB724705), Natural Science Foundation of Tianjin from Tianjin Municipal Science and Technology Commission, China (08JCZDJC17100), and Independent Innovation Foundation of Tianjin University, China.

摘要/Abstract

摘要：

渗透剂对蛋白质的稳定能力不仅与其极性表面积分率(f_pSA)有关, 而且也与其分子体积(V)密切相关. 因此对于渗透剂稳定蛋白质能力的分析, 需要同时考虑渗透剂的f_pSA和V. 为了考察渗透剂的f_pSA和V对稳定蛋白质能力的影响, 本文以胰凝乳蛋白酶抑制剂2(CI2)为模型蛋白, 首先利用分子动力学模拟, 考察了数种典型渗透剂对CI2 热稳定性的影响; 并根据模拟数据计算得到了渗透剂影响蛋白质热稳定性的一维结构参数; 然后利用统计学双参数拟合, 同时引入渗透剂的f_pSA和V, 建立了用于分析渗透剂稳定蛋白质能力的模型; 最后利用模型分析了渗透剂的f_pSA和V与其稳定蛋白质能力的关系. 研究发现: 利用分子动力学模拟结果定义并计算得到的一维结构参数能够较好地描述在热变性条件下渗透剂对CI2 的稳定能力;所建立的模型能够很好地分析渗透剂对蛋白质的稳定能力;并且由于V和f_pSA二次项的引入, 可大大提高仅以f_pSA为参数的模型的精度; 另外, 渗透剂对蛋白质的热稳定能力与其V成正比; 由于拟合公式中引入了f_pSA二次项, 在f_pSA小于0.7 时, f_pSA与渗透剂的稳定能力呈现负相关, 但当f_pSA大于0.7 时,其与渗透剂的稳定能力反而呈现正相关.

关键词: 分子动力学模拟, 蛋白质稳定性, 渗透剂, 极性表面积分率, 分子体积

Abstract:

We correlated the protective ability of osmolytes on proteins with their fractional polar surface area (f_pSA) and molecular volume (V). Thus, both parameters need to be considered when the protective ability of osmolytes is analyzed. We carried out molecular dynamics simulations of the chymotrypsin inhibitor 2 (CI2) in different osmolytes to probe the molecular basis of the stabilizing effect. Based on the simulation data, a one-dimensional structure parameter was first calculated. We then used a statistical bivariate fit model to obtain a theoretical model, which represents the stability capacity of the osmolytes. Finally, the model was used to analyze the correlation between the two parameters (f_pSA and V) and the protective ability of the osmolytes. We found that the one-dimensional structure parameter characterized the protective ability of the osmolytes well. Using this model, the protective stability of the osmolytes can be analyzed accurately. The inclusion of V and the two-order term of f_pSA greatly increases the accuracy of the model. The protective capacity of the osmolytes increases with V. In addition, we introduced the two-order term of f_pSA into the fit formula. We found that the f_pSA of the osmolytes is negatively correlated with its protective ability when it is less than 0.7. However, when the f_pSA of the osmolytes is larger than 0.7, it is positively correlated with its protective ability.

Key words: Molecular dynamics simulation, Protein stability, Osmolyte, Fractional polar surface area, Molecular volume

刘夫锋, 纪络, 董晓燕. 渗透剂的分子体积和极性表面积分率对胰凝乳蛋白酶抑制剂2热稳定性的影响[J]. 物理化学学报, 2010, 26(10), 2813-2820. doi: 10.3866/PKU.WHXB20101011

LIU Fu-Feng, JI Luo, DONG Xiao-Yan. Effects ofMolecular Volume and Fractional Polar Surface Area of Osmolytes on the Thermal Stability of Chymotrypsin Inhibitor 2[J]. Acta Phys. -Chim. Sin. 2010, 26(10), 2813-2820. doi: 10.3866/PKU.WHXB20101011

链接本文: https://www.whxb.pku.edu.cn/CN/10.3866/PKU.WHXB20101011

https://www.whxb.pku.edu.cn/CN/Y2010/V26/I10/2813

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渗透剂的分子体积和极性表面积分率对胰凝乳蛋白酶抑制剂2热稳定性的影响

Effects ofMolecular Volume and Fractional Polar Surface Area of Osmolytes on the Thermal Stability of Chymotrypsin Inhibitor 2

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