Thermodynamics protein-ligand interactions

Perozzo, R., Folkers, G., and Scapozza, L. (2004). Thermodynamics of protein-ligand interactions history, presence and future aspects. Journal of Receptor and Signal Transduction Research 24, 1-52. 

Helms V, Wade RC. Thermodynamics of water mediating protein-ligand interactions in cytochrome P450cam a molecular dynamics study. Biophys J 1995 69 810-824. 

Figure 4.6. Thermodynamic cycle for protein-ligand interactions. The experimentally measurable free energies are and AGbi di (horizontal),...

Understanding those components that influence the interfacial binding properties in protein/protein and protein/ligand interactions is of basic importance in protein chemistry. In this report, we have defined a system that should allow the dissection of those chemical properties that influence primary interactions via an evaluation of the transition-state thermodynamic components. 

Experimental Approaches to Determine the Thermodynamics of Protein-Ligand Interactions... 

This chapter provides a broad overview of the purpose and experimental approaches for determining thermodynamic parameters of protein-ligand interactions. 

The thermodynamic analyses most often used, particularly fhe van t Hoff mefhod, require that measurements be made at steady-state conditions. In the case of radioligand binding determination of equilibrium constants, fhe time required for fhe protein-ligand interaction to reach steady state depends on fhe incubation temperature, and, therefore, the equilibrium constant must be determined for each temperature studied. For the most accurate results, fhe determination needs to be made at more than two temperatures in order to detect non-linearity. The integrated form of the van t Hoff equation takes fhe simple form fhat is commonly used only if ATT and AS° for the interaction are not temperature dependent otherwise, non-linearity in the van t Hoff plot can arise. Meaningful information can StiU be obtained in such cases, but more complex analysis is required. 

Olsson TS et al (2008) The thermodynamics of protein-ligand interaction and solvation insights for ligand design. J Mol Biol 384(4) 1002-1017... 

So far there have been relatively few applications of electrophoresis at elevated hydrostatic pressures. However, this method has several advantages over other methods such as optical methods it is a simple and direct means of studying dissociation and denaturation processes, and of describing the thermodynamics of protein-ligand interactions. These qualitative and quantitative studies can be performed using small amounts of pure proteins or complex protein mixtures. In addition, this technique permits separation and subsequent isolation of the different protein conformational states or subunits. 

It appears that the most important attractive non-covalent forces for biological association in aqueous solution are electrostatic, dispersion and hydrophobic. Electrostatic interactions are probably more important in providing specificity than in contributing to the overall thermodynamic driving force for association. It is likely that dispersion is important and hydrophobic terms essential in most protein-ligand interactions. 

FIGURE 77 Thermodynamic protein-ligand model adapted for the successive inter-molecular connections of metal ions to a one-dimensional multisite receptor (adapted from Piguet et al., 2005). /f is the absolute affinity of site / for the entering lanthanide R, and is the intramolecular intermetallic interaction between two nearest neighbors. 

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