Gutheil W G
Department of Biochemistry, Tufts University School of Medicine, Boston, MA 02111.
Biophys Chem. 1992 Dec;45(2):181-91. doi: 10.1016/0301-4622(92)87010-g.
A model of the cooperative interaction of ligand binding to a dimeric protein is presented based upon the unique and independent parameters (UIP) thermodynamic formulation (Gutheil and McKenna, Biophys. Chem. 45 (1992) 171-179). The analysis is developed from an initial model which includes coupled conformational and ligand binding equilibria. This completely general model is then restricted to focus on conformationally mediated cooperative interactions between the ligands and the expressions for the apparent ligand binding constant and the apparent ligand-ligand interaction constant are derived. The conditions under which there is no cooperative interaction between the ligands are found as roots to a polynomial equation. Consideration of the distribution of species among the various conformational states in this general model leads to a set of inequalities which can be represented as a two dimensional plot of boundaries. By superimposing a contour plot of the value of the apparent ligand-ligand interaction constant over the plot of boundaries a complete graphical representation of this system is achieved similar to a phase diagram. It is found that the parameter space homologous to Koshland-Nemethy-Filmer type of model is most consistent with both positive and negative cooperativity in this model. The maximal amount of positive and negative cooperativity are found to be simple functions of Kc, the equilibrium constant associated with the change of a subunit and ligand from the unligated to ligated conformation. It is shown that under certain limiting conditions the apparent allosteric interaction between ligands is equal to the conformational interaction between subunits. The methods presented are generally applicable to the theoretical analysis of thermodynamic interactions in complex systems.
基于独特且独立的参数（UIP）热力学公式（古特尔和麦肯纳，《生物物理化学》45卷（1992年）171 - 179页），提出了一种配体与二聚体蛋白结合的协同相互作用模型。该分析从一个初始模型展开，该模型包括耦合的构象和配体结合平衡。然后将这个完全通用的模型进行限制，以专注于配体之间构象介导的协同相互作用，并推导了表观配体结合常数和表观配体 - 配体相互作用常数的表达式。发现配体之间不存在协同相互作用的条件是一个多项式方程的根。考虑这个通用模型中各种构象状态下物种的分布会导致一组不等式，这些不等式可以表示为边界的二维图。通过在边界图上叠加表观配体 - 配体相互作用常数的值的等高线图，实现了该系统类似于相图的完整图形表示。发现与科什兰德 - 内梅蒂 - 菲尔默类型模型同源的参数空间在该模型中与正协同性和负协同性最为一致。发现正协同性和负协同性的最大量是Kc的简单函数，Kc是与亚基和配体从未结合构象转变为结合构象相关的平衡常数。结果表明，在某些极限条件下，配体之间的表观变构相互作用等于亚基之间的构象相互作用。所提出的方法通常适用于复杂系统中热力学相互作用的理论分析。
