Binding free energy estimation

Our ultimate goal is to calculate an absolute binding score that is an approximation of the binding free energy. It is convenient to decompose the binding free energy estimate into three basic terms, the bound pose-dependent term and two pose-independent correction terms ... 

A logical work-around to the inaccuracy of fast scoring functions is the use of more rigorous binding free energy estimation methods for either prioritizing virtual hits... 

Hansson, T., Aqvist, J. Estimation of binding free energies for HIV proteinase inhibitors by molecular dynamics simulations. Prot. Eng. 8 (1995) 1137-1144... 

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... 

Hansson T and J Aqvist 1995. Estimation of Binding Free Energies for HIV Proteinase Inhibitors b Molecular Dynamics Simulations. Protein Engineering 8 1137-1144. 

The same technique can be used in some cases to obtain accurate estimates of binding free energy differences for a set of ligands of interest [25, 31-34]. The molecule taken as the reference need not be a real molecule. Indeed, the reference molecule could be intermediate between a large set of molecules of interest, so that conformations that are sufficiently representative of them all are sampled in the reference simulation. The justification for this approach is discussed in detail in Chap. 6. To achieve this for a variety of substituted phenols, Liu et al. [25] added dummy atoms to the ring at the sites they wished to substitute. Such dummy atoms can be softer ... 

The first version of the LIE method employed the linear response approximation to estimate the electrostatic part of the solvation/binding free energies. The linear response result for this component of the solvation... 

T. Hansson and J. Aqvist, Estimation of binding free energies for HIV proteinase... 

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