Ligand-protein binding thermodynamics

Euture improvements of the methods presented here will include modifications that enable determination of the thermodynamic parameters of protein-ligand binding interactions. Eor example, ALIS-based Kd or off-rate measurements at varying temperatures could yield useful relationships between chemical structures and binding thermodynamics. Ready access to such information, especially for targets that otherwise require complex bioassays for their study, could posi-... 

R. A. Alberty, Fundamental equation of thermodynamics for protein-ligand binding, Biophys. Chem. 104,543-559 (2003). 

This package shows how to calculate various thermodynamic properties of a protein-ligand binding. There are three ways to discuss the thermodynamics of the formation of Hav M02av ... 

Marchaj, A., Jacobsen, D. W., Savon, S. R., Brown, K. L. (1995). Kinetics and thermodynamics of the interaction of cyanocobalamin (vitamin Bjj) with haptocorrin Measurement of the highest protein-ligand binding constant yet reported, J. Am. Chem. Soc., 117 11640. 

Force fields were originally developed to simulate the conformational, thermodynamic and kinetic behaviors of small molecules or macromolecules much more efficiently, from a computer resource perspective, than quantum mechanical methods. It was hoped that if the interaction components of the force fields were applied to docking and scoring, the more accurate representation of the physics of protein ligand interactions would result in more accurate predictions of protein ligand binding affinities. 

Tang, L., Hopper, E.D., Tong, Y, et al. (2007) H/D exchange- and mass spectrometry-based strategy for the thermodynamic analysis of protein-ligand binding. Anal Chem, 79 (15), 5869-5877. 

R274 M. Akke, Conformational Dynamics and Thermodynamics of Protein-Ligand Binding Studied by NMR Relaxation , Biochem. Soc. Trans., 2012,40, 419. 

Fig. 2.9. The thermodynamic cycle used for the determination of protein-ligand relative binding free energies. Instead of carrying the horizontal transformations one can mutate the ligand in the free state - i.e., the left, vertical alchemical transformation , and in the bound state -i.e., the right, vertical alchemical transformation. This yields the difference in the binding free energies. AA I, jI,I j T. binding A mutation mutation...

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