Developing end-point methods for absolute binding free energy calculation using the Boltzmann-quasiharmonic model
Lauren Wickstrom, Emilio Gallicchio, Lieyang Chen, Tom Kurtzman, Nanjie Deng · Physical Chemistry Chemical Physics · 2022
. While the binding is accompanied by a significant reduction in the ligand translational/rotational entropy, the change in the torsional entropy in these host-guest systems is slightly positive. Compared with BQH, QHIC underestimates the reduction of configurational entropy because of the non-Gaussian probability distributions in the ligand rotation and a small number of torsions. The study highlights the crucial role of configurational entropy in determining binding and demonstrates the potential of using the new end-point method to provide insights in more complex protein-ligand systems.