de Carvalho Sidney Jurado, Ghiotto Renato Carlos Tonin, da Silva Fernando Luís Barroso
Departmento de Física, Instituto de Biociências, Letras e Ciências Extras, Universidade Estadual Paulista, 15054-000 - Rua Cristovão Colombo, 2265, Jd. Nazareth, São José do Rio Preto, SP, Brazil.
J Phys Chem B. 2006 May 4;110(17):8832-9. doi: 10.1021/jp054891e.
The understanding of electrostatic interactions is an essential aspect of the complex correlation between structure and function of biological macromolecules. It is also important in protein engineering and design. Theoretical studies of such interactions are predominantly done within the framework of Debye-Hückel theory. A classical example is the Tanford-Kirkwood (TK) model. Besides other limitations, this model assumes an infinitesimally small macromolecule concentration. By comparison to Monte Carlo (MC) simulations, it is shown that TK predictions for the shifts in ion binding constants upon addition of salt become less reliable even at moderately macromolecular concentrations. A simple modification based on colloidal literature is suggested to the TK scheme. The modified TK models suggested here satisfactorily predict MC and experimental shifts in the calcium binding constant as a function of protein concentration for the calbindin D(9k) mutant and calmodulin.
对静电相互作用的理解是生物大分子结构与功能之间复杂关联的一个重要方面。它在蛋白质工程与设计中也很重要。此类相互作用的理论研究主要是在德拜 - 休克尔理论框架内进行的。一个经典例子是坦福德 - 柯克伍德（TK）模型。除了其他局限性外，该模型假定大分子浓度无限小。与蒙特卡罗（MC）模拟相比，结果表明，即使在中等大分子浓度下，TK对加盐后离子结合常数变化的预测也变得不太可靠。基于胶体文献对TK方案提出了一种简单修改。这里提出的修改后的TK模型能够令人满意地预测钙结合蛋白D（9k）突变体和钙调蛋白的钙结合常数随蛋白质浓度变化而产生的MC和实验变化。
