The thermodynamics of binding

At a slightly more complicated level we use equation (18b) to obtain the inhibitor-enzyme and enzyme components of the relative binding free energy. These are given in columns 2 and 3 of Table 3. In the case of Ro31-8959, the wild type complex is 0.41 kcal/mol more stable than the mutant complex, hence the mutant complex is more likely to dissociate. The I84V enzyme is 0.74 kcal/mol more stable than the wild type enzyme, hence 

The calculated change in binding free energy due to mutation for the inhibitors Ro31-8959, A- 

and KNI-272 binding to wild-type HIV-1 protease and its I84V mutant. 

The inhibitor-enzyme and isolated enzyme components of the relative binding free energy are 

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Thus structural background suggests that the bound cyt c ccp adduct may actually consist of a distribution of structures. In this section, we consider the thermodynamics of binding cyt c and ccp, both for the native proteins, from different species, and proteins incorporating single site replacements, as prepared by site directed mutagenesis. 

In this study the physical parameters involved in interaction of a major class of meat flavorants, methyl pyrazines, with soy proteins were determined at meat roasting temperatures. Beef diffusate, the water soluble, low molecular weight fraction that constitutes about IX of beef, was shown to contain the necessary precursors to obtain a desirable, thermally generated meat aroma (8). Diffusate was heated under controlled conditions and generated volatiles were transferred to a gas chromatograph for separation and quantitation. Methyl pyrazines, either from heated diffusate or from standard solutions, were measured in the presence of purified soy proteins and the thermodynamics of binding were determined. 

There have been several studies of the thermodynamics of binding to poly(vinylpyrrolidone). ... 

This chapter has covered the thermodynamics of binding, analytical methods to determine binding constants, several classes of receptors used in molecular recognition studies, and supramolecular chemistry. Along with weak forces, the topics of this chapter could easily be expanded into a complete textbook, and an entire one- or two-semester course. Therefore, we have really only briefly introduced each of these topics. However, our discussion has been deep enough that we can take the concepts and apply them to many of the topics of the second part of this textbook. Examples of topics in the second part that use concepts from this chapter include measuring thermodynamic parameters, solvent effects on reaction kinetics, and the use of weak forces to control reaction stereochemistry. 

Talhout, R. and Engberts, J.B.F.N., Probing the effect of the amidinium group and the phenyl ring on the thermodynamics of binding ofbenzamidinium chloride to trypsin, Org. BiomoL Chem., 2004,2,3071-3074. 

In this article, we will explore the means by which molecules bind to enzymes and so behave as competitive inhibitors. We will then review the importance of pharmacophores in this process and the meth< used to identify, characterize, and search for pharmacophores. Finally, the role played by molecular flexibility, the thermodynamics of binding, and the impact of the pharmacophore concept upon drug design will be examined. 

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