Interaction of Lysozyme with a Dendritic Polyelectrolyte: Quantitative Analysis of the Free Energy of Binding and Comparison to Molecular Dynamics Simulations.
Interaction of Lysozyme with a Dendritic Polyelectrolyte: Quantitative Analysis of the Free Energy of Binding and Comparison to Molecular Dynamics Simulations.
复制标题
DOI：
10.1021/acs.jpcb.9b07448
复制
发表时间：
2019-09
期刊：
影响因子：
--
通讯作者：
Xiao Xu;M. Ballauff
中科院分区：
文献类型：
--
作者：
Xiao Xu;M. Ballauff
我们全面分析了水溶液中溶菌酶与树枝状聚甘油硫酸酯(DPGS)结合的能量学。该体系是研究蛋白质与聚电解质相互作用的理想模型。我们讨论并模拟了∆结合自由能G_b=-k_B T ln DPGS K_b作为两个决定变量，即盐浓度c_S和温度T的函数。溶菌酶/体系在整个温度范围内表现出很强的热熵补偿，类似于观察到的DNADNA与各种蛋白质的相互作用。根据Dragan等人的建议。[欧元。生物群落。J.(2017)46：301]自由能∆G_b可分解为∆G_b=∆G_Res+∆G_Ci，其中∆G_Ci表示反离子释放的部分，而∆G_res是将∆G_b外推到1M盐浓度得到的部分。DlogKb/dlogcs的曲线图可以得到完全的直线，这些直线可以外推到c_S=1m，以得到∆G_res。∆G_res和∆G_ci均可通过隐式溶剂分子动力学模拟得到，最大盐浓度为1M。在规定的误差范围内，实验和模拟结果吻合较好。此外，∆G_res是由dPG与溶菌酶之间的直接静电接触或盐桥作用引起的。由于∆G_Ci=-T∆S_Ci，其中∆S_Ci是反离子释放的熵，整个结合熵∆S_b可以分解为∆S_b=∆S_Ci+∆S_RES。结合热∆H_b与∆S_RES的关系图显示了dPGS/溶菌酶体系的一条完美的主曲线。这些发现表明，该体系的强焓-熵抵消完全是一种完全非静电现象，完全是由于水的溶剂化或去溶化。因此，在模型体系dPGS和溶菌酶上得到的结果与Dragan等人得出的结论完全一致。用于DNA与各种蛋白质的结合。
We present a comprehensive analysis of the energetics of the binding of lysozyme to dendritic polyglycerolsulfate (dPGS) in aqueous solution. This system is a perfect model for studying the interaction of proteins with polyelectrolytes. We discuss and model the free energy of binding ∆G_b=-k_B T ln K_b as the function of the two decisive variables, namely the salt concentration c_s and the temperature T. The system lysozyme/dPGS exhibits a strong enthalpy-entropy compensation throughout the entire range of temperature, similar to the one observed for the interaction of DNA with various proteins. Following a suggestion of Dragan et al. [Eur. Biophys. J. (2017) 46:301] the free energy ∆G_b can be split up into ∆G_b=∆G_res+ ∆G_ci where ∆G_ci denotes the part due to counterion release whereas ∆G_res is the part obtained by extrapolation of ∆G_b to 1M salt concentration. Plots of dlog KB/dlog cs lead to perfectly straight lines that can be extrapolated to c_s = 1M in order to obtain ∆G_res. Both ∆G_res and ∆G_ci can be independently obtained by implicit solvent molecular dynamics simulations done up to salt concentrations of 1M. Good agreement of experiment and simulation within prescribed limits of error is found. Moreover, ∆G_res is shown to be caused by direct unscreened electrostatic contacts or salt bridges between dPGS and lysozyme. Since ∆G_ci= -T∆S_ci where ∆S_ci is the entropy due to counterion release, the entire binding entropy ∆S_b can be split up as ∆S_b=∆S_ci+∆S_res. Plots of the binding enthalpy ∆H_b vs. ∆S_res lead to a perfect master curve for the system dPGS/lysozyme. These findings suggest that the strong enthalpy-entropy cancellation found for this system is an entirely non-electrostatic phenomenon solely due to solvatation or desolvation by water. Thus, the results obtained here on the model system dPGS and lysozyme are in full agreement with the conclusion drawn by Dragan et al. for the binding of DNA to various proteins.