Noncooperative binding

The binding of a ligand (L) to a protein molecule (E) can be described by the following equilibrium  

The stability of the EL complex is an intrinsic property of the atomic contacts made between the partners and so has a constant value, irrespective of their concentration. This value is defined by a dissociation constant (ifd) or an association constant where 

It cannot be sufficiently stressed that [EJf is the concentration of free binding sites on the protein, and [L]f is the concentration of free ligand. When a system is in equilibrium, the net concentrations of each of the three components do not change they are in a dynamic equilibrium (Winzor Sawyer, 1995 Engel, 1996). 

The cmcial values to be gained from binding experiments are the affinity of the binding sites and the concentration of such sites in the sample. The way in which the binding data are used entirely depends on the method used to collect them. 

This method depends on the ability to measure the concentration of free ligand [L]p or bound ligand [L]b (Scatchard, 1949 Scatchard etal, 1957). Methods of this t)q)e usually exploit differences between the molecular properties of the free ligand and the protein-ligand complex. 

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Another simplification can be made if all binding sites are independent (noncooperative binding) and they can be attributed to classes of identical sites. In protein-drug affinity studies the fraction of drug molecules bound (D4) per protein molecule (P) is given by... 

Despite their very short sequence (7 to 38 amino acid residues for the 12 histatins identified so far), the histidine-rich salivary protein histatins have also been reported to precipitate tannins, eventually more efficiently than proline-rich proteins, especially at neutral pH and high tannin concentration. A detailed NMR analysis of the binding between EGCG and histatin 5, a 24-mer that is very rich in basic His, Lys, and Arg residues ( 60%) and devoid of secondary structure, has revealed noncooperative binding of six to seven flavanol molecules with a dissociation constant of 1 mM (pH 3.0, 25°C). ... 

Figure 8 Cooperative and noncooperative binding of O2. (a) Binding curves of myoglobin and hemoglobin, (b) Hill plot of binding curves. The Hill coefficient munber is determined from the first derivative (slope) of the HiU plots...

Noncooperative binding of protein nonspecifically to an infinite lattice is described by the McGhee-von Hippel model where... 

These key equations can also be simplified to account for noncooperative binding and/or assuming that Ihe observed changes in physical properties are additive, as was done for 1 2 equilibria with (62)-(68). For noncooperative binding. 

The cooperativity fold a (physically understood as by how many times the affinity of the cooperative interaction is larger than a hypothetical, noncooperative binding event) measured by this method was calculated as 8.8 and 19.7 for sequential binding and sequential binding followed by a conformational change model, respectively. Authors of the study found that these two models give the best description of the interaction. 

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