Binding of Ligands

Binding of small molecules to large ones (macromolecules) could, in principle, be treated using the adsorption theories discussed in the foregoing sections. However, it is more common to present ligand binding in terms of the multiple equilibrium theory. 

Let P be a polymer molecule containing j independent, identical sites to bind ligand A. Then, for the first molecule of A that binds to P 

Because the binding sites are independent and identical, K, K2.Kj assume one single value, independent of the site where A binds. 

In general, it is impossible to determine the concentrations of each individual species P, PA, PA2. PA, but the average number v of moles of A bound per mole P is usually experimentally accessible. 

If the binding sites were not identical, but all different, j different forms of PA would exist. For PA2, there would be j(J - l)/2 distinguishable forms, and for PA -that number would be j(j - 1)0 - 2)... 0 - 0 - )(/ However, because of the assumption of identical sites, binding of A to any one of the j sites is equally probable. It implies that [PA] = /[PA ], where indicates a specific site out of the j sites on P. Let be the binding constant for each individual site, then [PA] = /fi[P][A] = /[PA ] = / (JP][A], and, hence 

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Weltin, E. Galculating Equilibrium Goncentrations for Stepwise Binding of Ligands and Polyprotic Acid-Base Systems, ... 

In these equations, MR3 4, MR, and MR4 are the molar refractivities of 3- and 4-substituents, of R-, and of 4-substituents, respectively. All the equations exhibited positive coefficients of the MR terms. This suggests that the dispersion forces of substituents are actually responsible for the binding of ligands to cyclodextrin. Eq. 14 shows that the stability of a-cyclodextrin-RCOO complexes increases linearly up to MR = 4.0 and then falls off linearly. 

Proteins, 109,110, 116.Seealso Enzymes Macromolecules average thermal amplitudes, MD simulations, 119 binding of ligands to, 120 dielectric relaxation time of, 122 electrostatic energies in, 122, 123-125 flexibility of, 209,221,226-227, 227 folding, 109,227... 

Two main apoptotic pathways have been identified in mammalian cells the extrinsic pathway that is activated by the binding of ligands to cell-surface death receptors, and the intrinsic pathway that involves the mitochondrial release of cytochrome cP The activation of extrinsic and intrinsic apoptotic pathways promotes the cleavage into the active form of the pro-caspase-8 and pro-caspase-9, respectively, that mainly determine the activation of effector caspase-3. ° The intrinsic pathway is the main apoptotic pathway activated by chemotherapeutic drugs, while the cytotoxic drug-induced activation of the extrinsic pathway is a more controversial issue. ... 

Figure 1. Simplified schematic of receptor-mediated signal transduction in neutrophils. Binding of ligand to the receptor activates a guanine-nucleotide-binding protein (G protein), which then stimulates phospholipase C. Phosphatidylinositol 4,5-bis-phosphate is cleaved to produce diacylglycerol (DAG) and inositol 1,4,5-trisphosphate (IP3). DAG stimulates protein kinase C. IP3 causes the release of Ca from intracellular stores, which results in an increase in the cytosolic Ca concentration. This increase in Ca may stimulate protein kinase C, calmodulin-dependent protein kinases, and phospholipase A2. Protein phosphorylation events are thought to be important in stimulating degranulation and oxidant production. In addition, ionic fluxes occur across the plasma membrane. It is possible that phospholipase A2 and ionic channels may be governed by G protein interactions. ...

How is the affinity of Rieske clusters for the binding of ligands (e.g., semiquinone) controlled, and what is the role of the exposed histidine residues ... 

The rate of leaving of a group is also dependent upon the other groups present and in particular the group trans to it (12). Table 6 gives some data. Whereas the thermodynamic data establish a stability order for binding of ligands... 

Some cytokine receptors can directly initiate signal transduction upon binding of ligand. In other cases additional elements are involved. For many receptors, the exact intracellular events triggered upon ligand binding remain to be elucidated. However, the molecular details of signal transduction pathways for others (e.g. the interferons) are now understood... 

Applications of Car-Parrinello Molecular Dynamics in Biochemistry - Binding of Ligands in Myoglobin... 

Despite all these studies of proteins and synthetic models, many essential aspects of the function of myoglobin and hemoglobin, e.g. the way the protein controls the binding of ligands (02, CO, and NO), the precise structure of the Fe-ligand bonds and the structure-spin-energy relationships at the active center, are a topic of debate [2]. 

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