New Coarse Variables for the Accurate Determination of Standard Binding Free Energies

To
improve sampling of the configurational entropy change upon
protein–ligand binding, we have introduced a new set of coarse
variables describing the relative orientation and position of the
ligand via a global macromolecular orientational
procedure, onto which geometrical restraints are applied. Evaluating
the potential of mean force for the different coarse variables, the
experimental standard binding free energy for three decapeptides associated
with the SH3 domain of the Abl kinase is reproduced quantitatively.