Comparison of calculation and experiment implicates significant electrostatic contributions to the binding stability of barnase and barstar
Comparison of calculation and experiment implicates significant electrostatic contributions to the binding stability of barnase and barstar
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DOI：
10.1016/s0006-3495(03)74453-1
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发表时间：
2003-07-01
影响因子：
3.4
通讯作者：
Zhou, HX
中科院分区：
文献类型：
--
作者：
Dong, F;Vijayakumar, M;Zhou, HX
通过泊松-玻尔兹曼模型，采用三种不同的方案研究了静电相互作用对 barnase 和 barstar 结合稳定性的贡献：a)，介电边界指定为蛋白质的范德华 (vdW) 表面，蛋白质介电常数 (epsilon(p)) 为 4； b)，介电边界指定为分子（即溶剂排除（SE））表面以及 epsilon(p) = 4； c)、“SE + epsilon(p) = 20”。 “vdW + epsilon(p) = 4”和“SE + epsilonp = 20”协议预测总体静电稳定，而“SE + epsilonp = 4”协议预测总体静电不稳定。 “vdW + epsilon(p) = 4”方案与实验最一致。它定量再现了观察到的 17 个突变中和结合界面内的带电残基的影响，以及测量的跨越界面的 6 个电荷对的耦合能，并合理地合理化了实验离子强度和结合常数的 pH 依赖性。相比之下，“SE + epsilonp = 4”方案预测电荷对的耦合能明显更大，而“SE + epsilon(p) = 20”方案没有预测任何 pH 依赖性。这项研究要求对不同的泊松-玻尔兹曼协议进行进一步审查，并证明基于特定计算协议得出静电贡献结论的潜在危险。
The contributions of electrostatic interactions to the binding stability of barnase and barstar were studied by the Poisson-Boltzmann model with three different protocols: a), the dielectric boundary specified as the van der Waals (vdW) surface of the protein along with a protein dielectric constant (epsilon(p)) of 4; b), the dielectric boundary specified as the molecular (i.e., solvent-exclusion (SE)) surface along with epsilon(p) = 4; and c), "SE + epsilon(p) = 20." The "vdW + epsilon(p) = 4" and "SE + epsilonp = 20" protocols predicted an overall electrostatic stabilization whereas the "SE + epsilonp = 4" protocol predicted an overall electrostatic destabilization. The "vdW + epsilon(p) = 4" protocol was most consistent with experiment. It quantitatively reproduced the observed effects of 17 mutations neutralizing charged residues lining the binding interface and the measured coupling energies of six charge pairs across the interface and reasonably rationalized the experimental ionic strength and pH dependences of the binding constant. In contrast, the "SE + epsilonp = 4" protocol predicted significantly larger coupling energies of charge pairs whereas the "SE + epsilon(p) = 20" protocol did not predict any pH dependence. This study calls for further scrutiny of the different Poisson-Boltzmann protocols and demonstrates potential danger in drawing conclusions on electrostatic contributions based on a particular calculation protocol.