Relative binding free energies

S. Miyamoto and P. A. Kollman. Absolute and relative binding free energy calculations of the interaction of biotin and its analogs with streptavidin using molecular dynamics/free energy perturbation approaches. Proteins, 16 226-245, 1993. 

Mark, A. E., Xu, Y., Liu, H., van Gunsteren, W. F. Rapid non-empirical approaches for estimating relative binding free energies. Acta Biochim. Polonica 42 (1995) 525-536... 

S Hirono, PA Kollman. Calculation of the relative binding free energy of 2 -GMP and 2 -AMP to ribonuclease T1 using molecular dynamics/free energy perturbation approaches. J Mol Biol 212 197-209, 1990. 

DM Perguson, RJ Radmer, PA Kollman. Determination of the relative binding free energies of peptide inhibitors to the HIV-1 protease. J Med Chem 34 2654-2659, 1991. 

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...

Computational analysis of binding site interactions is achieved by calculating the relative binding free energy (AAGbind) for a ligand L with an... 

Overall, the initial applications of MM-PBSA suggest that the method can effectively calculate the relative binding free energies in a number of protein-ligand complexes. However, there are a number of issues involving limitations or potential improvements in this methodology which we now discuss. 

The calculated relative binding free energies for AMP to sulfate (4) and AMP to carboxylate (5) mutations are 3.5 0.6 kcal/mol and 5.0 1.6 kcal/mol, respectively. These calculated free energies are qualitatively similar to the experimental results of >2.6 kcal/mol and >3.6 kcal/mol for... 

M. R. Reddy and M. D. Erion, Calculation of relative binding free energy differences for... 

The relative binding free energy change for the two substrates is computed using the second cycle (Figure 2), which is represented by the following equation ... 

Table 1. Relative binding free energies (kcal/mol) of inhibitors to HIV-1 protease.

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