Solvation Effects in Calculated Electrostatic Association Free Energies for the C3d-CR2 Complex and Comparison with Experimental Data
Solvation Effects in Calculated Electrostatic Association Free Energies for the C3d-CR2 Complex and Comparison with Experimental Data
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DOI：
10.1002/bip.21388
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发表时间：
2010-06-01
期刊：
影响因子：
2.9
通讯作者：
Morikis, Dimitrios
中科院分区：
文献类型：
--
作者：
Cheung, Alexander S.;Kieslich, Chris A.;Morikis, Dimitrios
补体系统是先天免疫系统的一个组成部分，参与清除体内的病原体。补体蛋白片段C3d与B或T细胞受体补体受体（CR） 2之间的关联是先天免疫和适应性免疫之间的重要联系。本研究的目的是通过理论计算静电自由缔合能来预测C3d和CR2突变体的缔合能力，并评估溶剂化效应在计算中的重要性。我们证明了计算的溶剂化自由能差和库仑自由能比溶液中的静电自由能更敏感，因此，在预测特定C3d和CR2突变体的结合力能力（相对于亲本蛋白）方面更准确。结果表明，预测的溶剂化自由能差与实验数据成正比关系，而预测的库伦缔合自由能与实验数据成反比关系。我们的结果为C3d-CR2结合的物理化学性质提供了新的见解。我们讨论了库仑、溶剂化和溶液静电缔合自由能的预测有效性，并将我们的方法推广到其他系统的理论诱变研究中。这是一项基础研究，旨在提高我们在分子水平上对免疫系统调节的理论基础的理解。这种见解可以作为设计具有定制特性的监管机构、疫苗和其他生物技术产品的基础。(C) 2010 Wiley期刊公司生物工程学报（英文版），2010。
The complement system is an integral part of the innate immune system that participates in the clearance of pathogens from the body. The association between complement protein fragment C3d and B or T cell-receptor complement receptor (CR) 2 represents a crucial link between innate and adaptive immunities. The goal of this study is to predict association abilities of C3d and CR2 mutants by theoretically calculating electrostatic free energies of association and to assess the importance of solvation effects in the calculations. We demonstrate that calculated solvation free energy differences and Coulombic free energies of association are more sensitive than electrostatic free energies of association in solution and, thus, more accurate in predicting previously published experimental data for the association abilities (relative to the parent proteins) of specific C3d and CR2 mutants. We show that a proportional relationship exists between the predicted solvation free energy differences and the experimental data, while an inversely proportional relationship exists between the predicted Coulombic free energies of association and the experimental data. Our results yield new insights into the physicochemical properties underlying C3d-CR2 asssociation. We discuss the predictive validity of We Coulombic, solvation, and solution electrostatic free energies of association and the generalization of our method for theoretical mutagenesis studies of other systems. This is a basic study, aimed toward improving our understanding of the theoretical basis of immune system regulation at the molecular level. Such insight can serve as the groundwork for the design of regulators with tailored properties, vaccines, and other biotechnology products. (C) 2010 Wiley Periodicals, Inc. Biopolymers 93: 509-519, 2010.