Dong Feng, Vijayakumar M, Zhou Huan-Xiang
Department of Physics, Florida State University, Tallahassee, Florida 32306, USA.
Biophys J. 2003 Jul;85(1):49-60. doi: 10.1016/S0006-3495(03)74453-1.
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 + epsilon (p) = 20" protocols predicted an overall electrostatic stabilization whereas the "SE + epsilon (p) = 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 + epsilon (p) = 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.
采用泊松-玻尔兹曼模型，通过三种不同的方案研究了静电相互作用对核糖核酸酶 barnase 和其抑制剂 barstar 结合稳定性的贡献：a），将介电边界指定为蛋白质的范德华（vdW）表面，同时蛋白质介电常数（ε(p)）为 4；b），将介电边界指定为分子（即溶剂排除（SE））表面，同时 ε(p) = 4；以及 c），“SE + ε(p) = 20”。“vdW + ε(p) = 4”和“SE + ε(p) = 20”方案预测了整体静电稳定作用，而“SE + ε(p) = 4”方案预测了整体静电去稳定作用。“vdW + ε(p) = 4”方案与实验结果最为一致。它定量再现了观察到的 17 个突变对结合界面处带电荷残基的中和作用，以及界面上六个电荷对的测量耦合能，并合理地解释了结合常数对实验离子强度和 pH 的依赖性。相比之下，“SE + ε(p) = 4”方案预测的电荷对耦合能明显更大，而“SE + ε(p) = 20”方案未预测到任何 pH 依赖性。这项研究要求对不同的泊松-玻尔兹曼方案进行进一步审查，并证明了基于特定计算方案得出关于静电贡献结论时的潜在危险。
