Free energies of binding

Since the net free energy change for the cycle is zero, the difference between the computable free energies for transforming L to if, when bound to protein and when dissolved in water, is equal to the difference between the measurable standard free energies of binding L and if to protein, i.e., the difference in affinity... 

Clearly, a free energy of binding computed with (9), (10) and (13) refers to a highly restricted state of the dissociated ligand. In order to convert such a free energy to a free energy relative to a normal standard state with volume per molecule Vg and no restriction on the molecular orientation, the following term must be added... 

Table 1. Computed free energies of binding of benzene to different rigid models of the protein.

Hermans, J., Wang, L. Inclusion of loss of translational and rotational freedom in theoretical estimates of free energies of binding. Application to a complex of benzene and mutant T4-lysozyme. J. Am. Chem. Soc. 119 (1997) 2707-2714... 

Jorgensen W L, J K Buckner, S Boudon and J Tirado-Reeves 1988. Efficient Computation of Absoluti Free Energies of Binding by Computer Simulations - Applications to the Methane Dimer ir Water. Journal of Chemical Physics 89 3742-3746. 

Binding and complexation data Folding processes Transition temperatures Free energies for point mutations Free energies of binding... 

WL Jorgensen, JK Buckner, S Boudon, J Tirado-Rives. Efficient computation of absolute free energies of binding by computer simulations. Application to the methane dimer m water. J Chem Phys 89 3742-3746, 1988. 

Quantum mechanical approaches, such as those applied by Merz [84], use traditional quantum mechanics to calculate free energies of binding. Though relatively successful, the computational time required to calculate the energies make this approach impractical to large data sets. 

Comparisons of affinity among different inhibitors for a common enzyme, or among different enzymes for a common inhibitor, are best done in terms of the relative dissociation constants or the related Gibbs free energy of binding. 

As we described in Chapter 3, the binding of reversible inhibitors to enzymes is an equilibrium process that can be defined in terms of the common thermodynamic parameters of dissociation constant and free energy of binding. As with any binding reaction, the dissociation constant can only be measured accurately after equilibrium has been established fully measurements made prior to the full establishment of equilibrium will not reflect the true affinity of the complex. In Appendix 1 we review the basic principles and equations of biochemical kinetics. For reversible binding equilibrium the amount of complex formed over time is given by the equation... 

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